In prokaryotes, the nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK []. The DnaK reaction cycle involves rapid peptide binding and release, which is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK, which enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK, which is required for peptide release. In eukaryotes, GrpE is essential for mitochondrial Hsp70 function, however the cytosolic Hsp70 homologues are GrpE-independent.GrpE binds as a homodimer to the ATPase domain of DnaK, and may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains, the N-terminal coiled coil domain, which may facilitate peptide release, and the C-terminal head domain, which forms part of the contact surface with the ATPase domain of DnaK. This superfamily represents the N-terminal coiled-coil domain.
This is the N-terminal domain of the SWI/SNF and RSC complexes subunit Ssr4 from S. pombe, a member of the chromatin structure remodeling complex (RSC) and the SWI/SNF complex [, ]. RSC is involved in transcription regulation and nucleosome positioning which controls, particularly, membrane and organelle development genes. The ATP-dependent chromatin remodelling complex SWI/SNF is required for the positive and negative regulation of gene expression of a large number of genes through the regulation of nucleosome remodelling [].The structure of this domain revealed that it has a novel fold comprising an antiparallel β-sheet of seven strands with α-helices on one side and random coil on the other []. It contains the highly conserved motif WxxxxxPxxGxxxxxxxxxxxxxxxDG.
Phosphoprotein P, an indispensable subunit of the viral polymerase complex, is a modular protein organised into two moieties that are both functionally and structurally distinct: a well-conserved C-terminal moiety that contains all the regions required for transcription, and a poorly conserved, intrinsically unstructured N-terminal moiety that provides several additional functions required for replication. The N-terminal moiety is responsible for binding to newly synthesised free N(0) (nucleoprotein that has not yet bound RNA), in order to prevent the binding of N(0) to cellular RNA. The C-terminal moiety consists of an oligomerisation domain, an N-RNA (nucleoprotein-RNA)-binding domain and an L polymerase-binding domain [, ]. The oligomerisation domain reveals a homotetrameric coiled coil structure with many details that are different from classic coiled coils with canonical hydrophobic heptad repeats [].This superfamily represents domain 1 of the phosphoprotein P oligomerisation domain from Sendai virus as well as from close family members.
Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree [].
FERM domain-containing protein 4A (FRMD4A) is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1 [].FERM domain-containing protein 4B (FRMD4B, also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signaling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signaling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins []. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [, ].
SRF-like/Type I subfamily of MADS (MCM1, Agamous, Deficiens, and SRF (serum response factor)) box family of eukaryotic transcriptional regulators []. Binds DNA and exists as hetero- and homo-dimers [, ]. Differs from the MEF-like/Type II subgroup mainly in position of the alpha 2 helix responsible for the dimerization interface. Important in homeotic regulation in plants and in immediate-early development in animals []. Also found in fungi [, ].Human serum response factor (SRF) is a ubiquitous nuclear protein important for cell proliferation and differentiation. SRF function is essential for transcriptional regulation of numerous growth-factor-inducible genes, such as c-fos oncogene and muscle-specific actin genes. A core domain of around 90 amino acids is sufficient for the activities of DNA-binding, dimerisation and interaction with accessory factors. Within the core is a DNA-binding region, designated the MADS box [], that is highly similar to many eukaryotic regulatory proteins: among these are MCM1, the regulator of cell type-specific genes in fission yeast; DSRF, a Drosophila trachea development factor; the MEF2 family of myocyte-specific enhancer factors; and the Agamous and Deficiens families of plant homeotic proteins.In SRF, the MADS box has been shown to be involved in DNA-binding and dimerisation []. Proteins belonging to the MADS family function as dimers, the primary DNA-binding element of which is an anti-parallel coiled coil of two amphipathic α-helices, one from each subunit. The DNA wraps around the coiled coil allowing the basic N-termini of the helices to fit into the DNA major groove. The chain extending from the helix N-termini reaches over the DNA backbone and penetrates into the minor groove. A 4-stranded, anti-parallel β-sheet packs against the coiled-coil face opposite the DNA and is the central element of the dimerisation interface. The MADS-box domain is commonly found associated with K-box region see ().
The NRL (for NPH3/RPT2-Like) family is formed by signaling molecules specificto higher plants. Several regions of sequence and predicted structuralconservation define members of the NRL family, with three domains being mostnotable: an N-terminal BTB domain, a centrally located NPH3domain, and a C-terminal coiled coil domain. The function of the NPH3 domainis not yet known [, , , , , , , ].Root phototropism protein 3 (RPT3), also known as nonphototropic hypocotyl 3 (NPH3), and root phototropism 2 (RPT2) () represent the founding members of a novel plant-specific family []. Three domains define the members of this family: an N-terminal BTB (broad complex, tramtrack, bric a brac) domain (), a centrally located NPH3 domain (), and a C-terminal coiled-coil domain.NPH3 assembles with CUL3 to form a E3 complex that ubiquitinates phototropin 1 (phot1) and modulates phototropic responsiveness [, ]. NPH3 is necessary for root and hypocotyl phototropisms, but not for the regulation of stomata opening or chloroplast relocation []. Coleoptile phototropism protein 1 (CPT1) is a rice orthologue of Arabidopsis NPH3 also required for phototropism []. This entry also includes DOT3 (AT5G10250) that is involved in shoot and primary root growth; DOT3 mutants produce an aberrant parallel venation pattern in juvenile leaves [].
Amelogenins, cell adhesion proteins, play a role in the biomineralisation ofteeth. They seem to regulate formation of crystallites during the secretorystage of tooth enamel development and are thought to play a major role inthe structural organisation and mineralisation of developing enamel. Theextracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins [].Circulardichroism studies of porcine amelogenin have shown that the proteinconsists of 3 discrete folding units []: the N-terminal region appears tocontain β-strand structures, while the C-terminal region displayscharacteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain arepetitive β-turn segment and a "β-spiral"between Gln112 and Leu138,which sequester a (Pro, Leu, Gln) rich region []. The β-spiraloffers a probable site for interactions with Ca2+ ions.Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplasticamelogenesis imperfecta, a disease characterised by defective enamel. A 9bpdeletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disruptingthe 16-residue (Met1-Ala16) amelogenin signal peptide [].
Endocytosis and intracellular transport involve several mechanistic steps: (1) for the internalisation of cargo molecules, the membrane needs to bend to form a vesicular structure, which requires membrane curvature and a rearrangement of the cytoskeleton; (2) following its formation, the vesicle has to be pinched off the membrane; (3) the cargo has to be subsequently transported through the cell and the vesicle must fuse with the correct cellular compartment.Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs)-domain, which is required for their in vivofunction and their ability to tubulate membranes []. The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases.
Endocytosis and intracellular transport involve several mechanistic steps: (1) for the internalisation of cargo molecules, the membrane needs to bend to form a vesicular structure, which requires membrane curvature and a rearrangement of the cytoskeleton; (2) following its formation, the vesicle has to be pinched off the membrane; (3) the cargo has to be subsequently transported through the cell and the vesicle must fuse with the correct cellular compartment.Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs)-domain, which is required for their in vivofunction and their ability to tubulate membranes []. The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases. This entry identifies several fungal BAR domain-containing proteins, such as Gvp36, that are not detected by [].
It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation [, ].The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the cell-cycle-regulated cohesion of microtubule-organizing centres. This 281kDa protein consists mainly of domains predicted to form coiled coil structures. The C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes []. During interphase, C-Nap1 localizes to the proximal ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis [].
Bacterial GreA and GreB promote transcription elongation by stimulating an endogenous, endonucleolytictranscript cleavage activity of the RNA polymerase, allowing RNA transcription to continue past template-encoded arresting sites. GreA and GreB are sequence homologues and have homologues inevery known bacterial genome. GreA and GreB stimulate transcriptcleavage in different ways; GreA induces cleavage of 3'-RNA fragments 2-3 nt in length and can only preventthe formation of arrested complexes, whereas GreB induces cleavage of fragments up to 18 nt in length and canrescue preexisting arrested complexes [].A 15 Angstrom resolution helical reconstruction of the Escherichia coli core RNA polymerase (RNAP)/GreB complex that allows fitting of high-resolution RNAP andGreB structures. The model of the complex reveals a remarkable binding mode for GreB; the globular C-terminal domain binds RNAP at the edge of the active site channel, while the N-terminal coiled-coil domain extends 45 Angstrom into a channel directly to theRNAP active site. The results point to a key role for conserved acidic residues at the tip of the Gre factor coiled coil in modifying the RNAP active site to catalyse the transcript cleavage reaction, and mutational studies confirm that these positions are critical for Gre factor function. Functional differences between GreA and GreB correlate with the distribution of positively charged residues on one face of the N-terminal coiledcoil.
Bacterial GreA and GreB promote transcription elongation by stimulating an endogenous, endonucleolytictranscript cleavage activity of the RNA polymerase (RNAP) [], allowing RNA transcription to continue past template-encoded arresting sites. GreA and GreB are sequence homologues and have homologues inevery known bacterial genome. GreA and GreB stimulate transcriptcleavage in different ways; GreA induces cleavage of 3'-RNA fragments 2-3 nt in length and can only preventthe formation of arrested complexes, whereas GreB induces cleavage of fragments up to 18 nt in length and canrescue pre-existing arrested complexes.The 2.2 Angstrom resolution crystal structure of Escherichia coli GreA comprises an N-terminalantiparallel α-helical coiled coil, and a C-terminal globular domain. While theC-terminal domain binds RNAP, theN-terminal coiled coil interacts with the transcript 3' end and is responsible for stimulating the transcriptcleavage reaction []. Functional differences between GreA and GreB correlate with the distribution of positively charged residues onone face of the N-terminal coiled coil.Because members of the family outside the Proteobacteria resemble GreA more closely than GreB, the GreB clade () forms a plausible outgroup and the remainder of the GreA/B family, included in this family, is designated GreA. In the Chlamydias and some spirochetes, the conserved region of these proteins is found as the C-terminal region of a much larger protein.
Stathmin [](from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules []. However, when phosphorylated, its destabilisation ability is significantly reduced []. The stathmin family also includes:Stathmin 2 (Protein SCG10); a neuron-specific, membrane-associated proteinthat accumulates in the growth cones of developing neurons. It is highlysimilar in its sequence to stathmin, but differs in that it contains anadditional N-terminal hydrophobic segment of 32 residues which is probablyresponsible for its interaction with membranes.Stathmin 3 (SCG10-like protein; SCLIP) []; a protein specificallyexpressed in neurons.Stathmin 4 (Stathmin-like protein B3); which contains an additional N-terminal hydrophobic domain [].These proteins possess a stathmin-like domain (SLD) with various N-terminal extensions. SLD is a highly conserved domain of 149 amino acid residues. Structurally, it consists of an N-terminal domain of about 45 residues followed by a 78 residue α-helical domain consisting of a heptad repeat coiled coil structure and a C-terminal domain of 25 residues [, ]. The SLD binds two tubulins arranged longitudinally, head-to-tail, in protofilament-like complexes.
Calsequestrin contains three redox inactive TRX-fold domains [, ]. This entry represents the C-terminal TRX-fold domain.Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree [].
Calsequestrin contains three redox inactive TRX-fold domains [, ]. This entry represents the middle TRX-fold domain.Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree [].
Calsequestrin contains three redox inactive TRX-fold domains [, ]. This entry represents the N-terminal TRX-fold domain.Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree [].
The exact function of the Hepatitis C non-structural 5A (NS5A) protein is not known, but it is an active component of the replicase, regulates replication and modulates a range of cellular processes including innate immunity and dysregulated cell growth. NS5A is organised into three domains, labelled I, II and III. Domain I contains a zinc-binding motif and an amphipathic N-terminal helix which promotes membrane association. Mutations disrupting either the membrane anchor or zinc binding are lethal for RNA replication [, ].This entry represents the 1b domain of NS5A. It consists of two distinct anti-parallel β-sheets surrounded by extensive random coil structures []. This domain contains a disulphide bond near its C-terminal not required for the RNA replicase functions of NS5A. The presence of the cited sulphide bond suggests that it is likely responsible of the structural arrangement of domains II and III, thus playing a regulatory role in NS5A function by serving as a conformation switch to modulate functions of NS5A in and out of the replicase [].
Stathmin [](from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules []. However, when phosphorylated, its destabilisation ability is significantly reduced []. Stathmin is a highly conserved protein. Structurally, it consists of an N-terminal domain of about 45 residues followed by a 78 residue α-helical domain consisting of a heptad repeat coiled coil structure and a C-terminal domain of 25 residues.The stathmin family also includes:Stathmin 2 (Protein SCG10); a neuron-specific, membrane-associated proteinthat accumulates in the growth cones of developing neurons. It is highlysimilar in its sequence to stathmin, but differs in that it contains anadditional N-terminal hydrophobic segment of 32 residues which is probablyresponsible for its interaction with membranes.Stathmin 3 (SCG10-like protein; SCLIP) []; a protein specificallyexpressed in neurons.Stathmin 4 (Stathmin-like protein B3); which contains an additional N-terminal hydrophobic domain [].This entry represents stathmin-2 (also known as SCG10).
The TCR complex of T-lymphocytes consists of either a TCR alpha/beta or TCR gamma/delta heterodimer co-expressed at the cell surface with the invariant subunits of CD3 labelled gamma, delta, epsilon, zeta, and eta []. The zeta subunit forms either homodimers or heterodimers with eta [], but eta homodimers have not been observed. The structure of the zetazeta transmembrane dimer consists of a left-handed coiled coil with polar contacts. Two aspartic acids are critical for zetazeta dimerisation and assembly with TCR []. The high affinity immunoglobulin epsilon receptor (IgE Fc receptor) subunit gamma associates with a variety of FcR alpha chains to form a functional signaling complex. The gamma subunit has a critical role in allowing the IgE Fc receptor to reach the cell surface and regulates several aspects of the immune response []. It has significant structural homology to CD3 zeta and the related CD3 eta subunit and can facilitate T cell receptor expression and signaling in the absence of CD3 zeta and CD3 eta [].This family includes both CD3 zeta subunits and IgE Fc receptor gamma subunits.
The subfamily Paramyxovirinae of the family Paramyxoviridae now contains as main genera the Rubulaviruses, avulaviruses, respiroviruses, Henipavirus-es and morbilliviruses. Protein P is the best characterised, structurally of the replicative complex of N, P and L proteins and consists of two functionally distinct moieties, an N-terminal PNT, and a C-terminal PCT []. The P protein is an essential part of the viral RNA polymerase complex formed from the P and L proteins []. P protein plays a crucial role in the enzyme by positioning L onto the N/RNA template through an interaction with the C-terminal domain of N. Without P, L is not functional.The C-terminal part of P (PCT) is only functional as an oligomer and forms with L the polymerase complex. PNT is poorly conserved and unstructured in solution while PCT contains the oligomerisation domain (PMD) that folds as a homotetrameric coiled coil containing the L binding region and a C-terminal partially folded domain, PX (residues 474 to 568), identified as the nucleocapsid binding site. Interestingly, PX is also expressed as an independent polypeptide in infected cells. PX has a C-subdomain (residues 516 to 568) that consists of three {alpha}-helices arranged in an antiparallel triple-helical bundle linked to an unfolded flexible N-subdomain (residues 474 to 515).
Stathmin [](from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules []. However, when phosphorylated, its destabilisation ability is significantly reduced []. The stathmin family also includes:Stathmin 2 (Protein SCG10); a neuron-specific, membrane-associated proteinthat accumulates in the growth cones of developing neurons. It is highlysimilar in its sequence to stathmin, but differs in that it contains anadditional N-terminal hydrophobic segment of 32 residues which is probablyresponsible for its interaction with membranes.Stathmin 3 (SCG10-like protein; SCLIP) []; a protein specificallyexpressed in neurons.Stathmin 4 (Stathmin-like protein B3); which contains an additional N-terminal hydrophobic domain [].These proteins possess a stathmin-like domain (SLD) with various N-terminal extensions. SLD is a highly conserved domain of 149 amino acid residues. Structurally, it consists of an N-terminal domain of about 45 residues followed by a 78 residue α-helical domain consisting of a heptad repeat coiled coil structure and a C-terminal domain of 25 residues [, ]. The SLD binds two tubulins arranged longitudinally, head-to-tail, in protofilament-like complexes.
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].
Ketol-acid reductoisomerase (KARI; ()), also known as acetohydroxyacid isomeroreductase (AHIR or AHAIR), catalyzes the conversion ofacetohydroxy acids into dihydroxy valerates in the second step of thebiosynthetic pathway for the essential branched-chain amino acids valine,leucine, and isoleucine. KARI catalyzes an unusual two-step reactionconsisting of an alkyl migration in which the substrate, either 2-acetolactate(AL) or 2-aceto-2-hydroxybutarate (AHB), is converted to 3-hydoxy-3-methyl-2-oxobutyrate or 3-hydoxy-3-methyl-2-pentatonate, followed by a NADPH-dependentreduction to give 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylvalerate respectively [, , , , , ].KARI is present only in bacteria, fungi, and plants, but not in animals. KARIsare divided into two classes on the basis of sequence length andoligomerization state. Class I KARIs are ~340 amino acid residues in lengthand include all fungal KARIs, whereas class II KARIs are ~490 residues longand include all plant KARIs. Bacterial KARIs can be either class I or classII. KARIs are composed of two types of domains, an N-terminal Rossmann folddomain and one or two C-terminal knotted domains. Two intertwinned knotteddomains are required for function, and in the short-chain or class I KARIs,each polypeptide chain has one knotted domain. As a result, dimerization oftwo monomers forms two complete KARI active sites. In the long-chain or classII KARIs, a duplication of the knotted domain has occurred and, as a result,the protein does not require dimerization to complete its active site[, , , , , ].The α-helical KARI C-terminal knotted domain can be described as a six-helix core in which helices coil like cable threads around each other, thusforming a bundle [, , , , ].
Clathrin is a triskelion-shaped cytoplasmic protein that polymerises into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. Clathrin functions as a trimer, and these trimers, or triskelions, are comprised of three legs joined by a central vertex. Each leg consists of one heavy chain and one light chain. The clathrin heavy-chain contains a 145-residue repeat that is present in seven copies [, ]. The clathrin heavy-chain repeat (CHCR) is also found in nonclathrin proteins such as Pep3, Pep5, Vam6, Vps41, and Vps8 from Saccharomyces cerevisiae and their orthologs from other eukaryotes [, , , ]. These proteins, like clathrins, are involved in vacuolar maintenance and protein sorting. The CHCR repeats in these proteins could mediate protein-protein interactions, or possibly represent clathrin-binding domains, or perform clathrin-like functions. CHCR repeats in the clathrin heavy chain, Saccharomyces cerevisiae Vamp2 and human Vamp6 have been implicated in homooligomerization, suggesting that this may be the primary function of this repeat.The CHCR repeat folds into an elongated right-handed superhelix coil of short α-helices []. Individual 'helix-turn-helix-loop' or helix hairpin units comprise the canonical repeat and stack along the superhelix axis to form a single extended domain. The canonical hairpin repeat of the clathrin superhelix resembles a tetratrico peptide repeat (TPR), but is shorter and lacks the characteristic spacing of the hydrophobic residues in TPRs.
This entry represents the oligomerisation domain of the breakpoint cluster region oncoprotein Bcr, and the Bcr/Abl (Abelson-leukemia-virus) fusion protein created by a reciprocal (9;22) fusion []. Brc displays serine/threonine protein kinase activity (), acting as a GTPase-activating protein for RAC1 and CDC42. Brc promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them []. The Bcr/Abl fusion protein loses some of the regulatory function of Bcr with regards to small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells [].The Bcr, Bcr/Abl oncoprotein oligomerisation domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerisation domain is essential for the oncogenicity of the Bcr-Abl protein [].
Structural maintenance of chromosomes protein 1A (SMC1A) is a homologue of the yeast Smc1 protein, which is a component of the cohesin complex required for sister chromatid cohesion []. In human, it is part of the core cohesion complex composed of SMC1A, SMC3, RAD21 and STAG proteins []. These proteins form a ring structure that encircles sister chromatids to mediate sister chromatid cohesion []. SMC1A binds to SMC3 through its hinge domain []. Besides sister chromatid cohesion function, SMC1A-SMC3 heterodimer can also found in the RC-1 complex, a mammalian protein complex that promotes repair of DNA gaps and deletions through recombination [, ]. This entry also includes Smc1 homologue from Caenorhabditis elegans, SMCL-1. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis []. Mutations in SMC1A gene cause Cornelia de Lange syndrome 2 (CDLS2), which is a form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems [, ].
CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region [].
Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies []. These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in spruce budworm, Choristoneura fumiferana.The structure of these AFPs consists of a left-handed β-helix with 15 residues per coil []. The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs.A second insect antifreeze from Tenebrio molitor () also consists of β-helices, however in these proteins the helices form a right-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well.
Many microorganisms, such as methanogenic, acetogenic, nitrogen-fixing, photosynthetic, or sulphate-reducing bacteria, metabolise hydrogen. Hydrogen activation is mediated by a family of enzymes, termed hydrogenases, which either provide these organisms with reducing power from hydrogen oxidation, or act as electron sinks. There are two hydrogenases families that differ functionally from each other: NiFe hydrogenases tend to be more involved in hydrogen oxidation, while Iron-only FeFe (Fe only) hydrogenases in hydrogen production. Fe only hydrogenases () can either be monomeric and cytoplasmic or heterodimeric and periplasmic, being involved in either hydrogen production or uptake, respectively. This entry represents the small subunit of the heterodimeric enzyme, which is comprised of alternating random coil and alpha helical structures that encompass the large subunit in a novel protein fold [].A domain homologous to the small subunit is found at the C terminus of iron-only hydrogenase-like protein 1 (IOP1) and IOP2 (also known as nuclear prelamin A recognition factor), two orthologue proteins found in mammalian cells. IOP1 has been shown to be involved in mammalian cytosolic Fe-S protein maturation [].
CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region [].
CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region [].
LRP chaperone MESD (also known as mesoderm development candidate 2) represents a set of highly conserved proteins found from nematodes to humans. It is a chaperone that specifically assists with the folding of β-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). It also acts as a modulator of the Wnt pathway, since some LDLRs are coreceptors for the canonical Wnt pathway and is essential for specification of embryonic polarity and mesoderm induction []. The Drosophila homologue, known as boca, is an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members [].The final C-terminal residues, KEDL, are the endoplasmic reticulum retention sequence as it is an ER protein specifically required for the intracellular trafficking of members of the low-density lipoprotein family of receptors (LDLRs) []. The N- and C-terminal sequences are predicted to adopt a random coil conformation, with the exception of an isolated predicted helix within the N-terminal region, The central folded domain flanked by natively unstructured regions is the necessary structure for facilitating maturation of LRP6 (Low-Density Lipoprotein Receptor-Related Protein 6 Maturation) [].
This is the N-terminal region of MukB. MukB is involved in the segregation and condensation of prokaryotic chromosomes. MukE () along with MukF () interact with MukB in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli []. The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC []. ScpA () and ScpB () have little sequence similarity to MukE or MukF, though they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions. The structure of the N-terminal domain consists of an antiparallel six-stranded beta sheet surrounded by one helix on one side and by five helices on the other side []. It contains an exposed Walker A loop in an unexpected helix-loop-helix motif. In other proteins, Walker A motifs generally adopt a P loop conformation as part of a strand-loop-helix motif embedded in a conserved topology of alternating helices and (parallel) beta strands [].
Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2), also known as MAYP, belongs to the PCH (Pombe Cdc15 homology) family of proteins involved in the regulation of actin-related functions, including cell adhesion and motility []. In mice, it regulates F-actin bundling and enhances filopodia formation and motility in macrophages []. It may play an anti-inflammatory role in macrophages [].Pombe Cdc15 homology (PCH) family proteins were initially identified as adaptor proteins involved in the regulation of cytokinesis and actin dynamics []. They share a similar domain architecture, consisting of an N-terminal FCH domain followed by a coiled coil (CC) region and by one or two C-terminal SH3 domains. However, in some family members the SH3 domain is absent (FCHO1, FCHO2 and PSTPIP2) or there are tissue-specific alternatively spliced isoforms with and without an SH3 domain (CIP4b, CIP4c, CIP4V, Fbp17b). PCH family proteins interact with receptors, adaptors, enzymes and structural proteins to regulate their localisation and activity. Through these interactions, PCH proteins regulate cell morphology and motility, organelle integrity, protein trafficking and the organisation of the actin cytoskeleton [].
This family represents ScpB, which along with ScpA () interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation [, ]. The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli [], where MukB () is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE () or MukF (), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions. In general scpA and scpB form an operon in most bacterial genomes. Flanking genes are highly variable suggesting that the operon has moved throughout evolution. Bacteria containing an smc gene also contain scpA or scpB but not necessarily both. An exception is found in Deinococcus radiodurans, which contains scpB but neither smc nor scpA. In the archaea the gene order SMC-ScpA is conserved in nearly all species, as is the very short distance between the two genes, indicating co-transcription of the both in different archaeal genera and arguing that interaction of the gene products is not confined to the homologues in Bacillus subtilis. It would seem probable that, in light of all the studies, SMC, ScpA and ScpB proteins or homologues act together in chromosome condensation and segregation in all prokaryotes [].
This superfamily represents a subdomain known as domain D found at the C terminus of Tip20, which is part of the Dsl1p vesicle tethering complex essential for trafficking from the Golgi apparatus to the ER. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains []. Subunits of the vesicle tethering complex (such as Tip20 and Dsl1) share protein sequence similarity with known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. Proteins containing this domain includes EXOC6/PINT-1 from animals, Tip20 from budding yeast, Sec15 from fission yeasts and MAIGO2 (Mag2) from plants. Sec15 (EXOC6 homologue) is an exocyst complex component that links Sec4 and downstream fusion effectors at discrete cellular locations. Its C-terminal domain mediates Rab GTPases binding which occurs in a GTP-dependent manner []. PINT-1/Tip20/MAIGO2 play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER. They share a similar domain organisation with an N-terminal leucine heptad repeat rich coiled coil and an ~500-residue C-terminal RINT1/TIP20 domain, which might be a protein-protein interaction module necessary for the formation of functional complexes.
Subunits of the vesicle tethering complex (such as Tip20 and Dsl1) share protein sequence similarity with known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. Proteins containing this domain includes EXOC6/PINT-1 from animals, Tip20 from budding yeast, Sec15 from fission yeasts and MAIGO2 (Mag2) from plants. Sec15 (EXOC6 homologue) is an exocyst complex component that links Sec4 and downstream fusion effectors at discrete cellular locations. Its C-terminal domain mediates Rab GTPases binding which occurs in a GTP-dependent manner []. PINT-1/Tip20/MAIGO2 play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER. They share a similar domain organisation with an N-terminal leucine heptad repeat rich coiled coil and an ~500-residue C-terminal RINT1/TIP20 domain, which might be a protein-protein interaction module necessary for the formation of functional complexes. This superfamily represents the domain 1 found in the C-terminal domain of the exocyst complex subunit Sec15.
Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies []. These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in spruce budworm, Choristoneura fumiferana.The structure of these AFPs consists of a left-handed β-helix with 15 residues per coil []. The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs.A second insect antifreeze from Tenebrio molitor () also consists of β-helices, however in these proteins the helices form a right-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well.
Tripartite motif-containing protein 63 (TRIM63), also known as MURF-1 is an E3 ubiquitin-protein ligase involved in ubiquitin-mediated muscle protein turnover [, ]. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity []. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain []. It also participates in muscle stress response pathways and gene expression [, ]. MuRF-1 belongs to the C-II subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbours a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains [].This entry represents the C3HC4-type RING-HC finger found in TRIM63.
Members of the TCP family of transcription factors have so far only been found in plants, where they are implicated in processes related to cell proliferation. It appears that TCP domain (see ) protein have been recruited during evolution to control cell division and growth in various developmental processes. The TCP proteins fall into two subfamilies, one including CYC and TB1 and the other including the PCFs. Most members of the CYC/TB1 subfamily have an R domain, predicted to form a coiled coil that may mediate protein-protein interactions [, ].The R domain is rich in polar residues (arginine, lysine and glutamic acid) and is predicted to form a hydrophilic α-helix [].Some proteins known to contain an R domain are listed below:Antirrhinum majus (Garden snapdragon) cycloidea (CYC). It is involved in the control of floral symmetry, a character that has changed many times during plant evolutionZea mays (Maize) teosinte branched 1 (TB1). It controls the developmental of apical dominance that contributed to the evolution of modern day maize from its wild ancestor teosinte Arabidopsis thaliana (Mouse-ear cress) TCP2 and TCP3, which correlate with actively dividing regions of the floral meristem
This superfamily represents a structural domain which consists of three α-helices, including the arfaptin homology (AH) domain and the BAR (Bin-Amphiphysin-Rvs) domain.The arfaptin homology (AH) domain is a protein domain found in a range of proteins, including arfaptins, protein kinase C-binding protein PICK1 []and mammalian 69kDa islet cell autoantigen (ICA69) []. The AH domain of arfaptin has been shown to dimerise and to bind Arf and Rho family GTPases [, ], including ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The AH domain consists of three α-helices arranged as an extended antiparallel α-helical bundle. Two arfaptin AH domains associate to form a highly elongated, crescent-shaped dimer [, ].Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs) domain, which is required for their in vivofunction and their ability to tubulate membranes []. The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases.
TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response [, , ]. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair []. It also regulates CHD3 nucleosome remodelling during the DNA double-strand break (DSB) response []. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response []. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription []. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase []. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization []. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity [, ].This entry represents the RING-HC finger found in TIF1-beta.
TRIM54, also known as MuRF-3, is an E3 ubiquitin-protein ligase involved in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, and is developmentally upregulated, associates with microtubules, the sarcomeric M-line (this report) and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI) [, , ]. MuRF-3 belongs to the C-II subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbours a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.This entry represents the C3HC4-type RING-HC finger found in MuRF-3 (TRIM54).
Several proteins that contain RING fingers also contain a well-conserved40-residue cysteine-rich domain termed a B-box zinc finger. Often, one or two copies of the B-box are associated with a coiled coil domain in additionto the ring finger, forming a tripartite motif. The tripartite motif is found in transcription factors, ribonucleoproteins and proto-oncoproteins,but no function has yet been ascribed to the domain [].The solution structure of the B-box motif has been determined by NMR. The protein is a monomer, with 2 β-strands, 2 helical turns and 3extended loop regions packed in a novel topology []. Of 7 potential zincligands, only 4 are used, binding a single zinc atom in a C2-H2 tetrahedral arrangement. The B-box structure differs in tertiary fold from allother known zinc-binding motifs.A group of proteins that contain the B-box motif also host a well conserveddomain of unknown function. Proteins that include this domain are,e.g.: butyrophilin, the RET finger protein, the 52kDa Ro protein and theXenopus nuclear factor protein. The C-terminal portion of this region hasbeen termed the SPRY domain (after SPla and the RYanodine Receptor) [].
This entry represents the SH3 domain of proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1).Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) belongs to the PCH family. It interacts with Wiskott-Aldrich syndrome protein (WASP) and PTPN12, which are important regulators of the cytoskeleton and cell migration, suggesting that PSTPIP1 functions in these pathways []. PSTPIP1 has been identified as a component of the leukocyte uropod that regulates endocytosis and cell migration []. It also controls extracellular matrix degradation and filopodia formation in macrophages []. It interacts with pyrin, a protein that associates with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis []. Mutations in the PSTPIP1 gene have been linked to PAPA syndrome, an inflammatory disease [].Pombe Cdc15 homology (PCH) family proteins were initially identified as adaptor proteins involved in the regulation of cytokinesis and actin dynamics []. They share a similar domain architecture, consisting of an N-terminal FCH domain followed by a coiled coil (CC) region and by one or two C-terminal SH3 domains. However, in some family members the SH3 domain is absent (FCHO1, FCHO2 and PSTPIP2) or there are tissue-specific alternatively spliced isoforms with and without an SH3 domain (CIP4b, CIP4c, CIP4V, Fbp17b). PCH family proteins interact with receptors, adaptors, enzymes and structural proteins to regulate their localisation and activity. Through these interactions, PCH proteins regulate cell morphology and motility, organelle integrity, protein trafficking and the organisation of the actin cytoskeleton [].
This entry represents the oligomerisation domain of the breakpoint cluster region oncoprotein Bcr, and the Bcr/Abl (Abelson-leukemia-virus) fusion protein created by a reciprocal (9;22) fusion []. Brc displays serine/threonine protein kinase activity (), acting as a GTPase-activating protein for RAC1 and CDC42. Brc promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them []. The Bcr/Abl fusion protein loses some of the regulatory function of Bcr with regards to small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells [].The Bcr, Bcr/Abl oncoprotein oligomerisation domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerisation domain is essential for the oncogenicity of the Bcr-Abl protein [].
AAA proteases are ATP-dependent metallopeptidases present in eubacteria as well as in organelles of bacterial origin, i.e., mitochondria and chloroplasts. The AAA proteases are also known as FtsH, referring to the Escherichia coli enzyme (Filamentous temperature sensitive H). Most bacteria have a single gene encoding FtsH, three genes are present in yeast and humans, while 12 orthologs have been found in the genome of plants [].E. coil FtsH is a membrane-anchored ATP-dependent protease that degrades misfolded or misassembled membrane proteins as well as a subset of cytoplasmic regulatory proteins. FtsH is a 647-residue protein of 70kDa, with two putative transmembrane segments towards its N terminus which anchor the protein to the membrane, giving rise to a periplasmic domain of 70 residues and a cytoplasmic segment of 520 residues containing the ATPase and protease domains [].The main function of organellar AAA/FtsH proteases is selective degradation of non-assembled, incompletely assembled and/or damaged membrane-anchored proteins. Additional functions of the AAA/FtsH proteases that are not directly connected with protein quality control are processing of pre-proteins, dislocation of membrane proteins or degradation of regulatory proteins [, , ].
N-terminal RING finger/B-box/coiled coil (RBCC) or tripartite motif (TRIM) proteins, which are found in metazoa, are involved in a vast array of intracellular functions. They appear to function as part of large protein complexes and possess ubiquitin-protein isopeptide ligase activity. The following RBCC proteins contain an ~60-residue COS (C-terminal subgroup one signature) domain, which is also found in a distantly related non-RBCC microtubule-binding protein, GLFND:Vertebrate MID1 and MID2, which associate with microtubules through homo- and heterodimerizationAnimal TRIM9, which plays a regulatory role in synaptic vesicle exocytosisMammalian TRIM nine-like (TNL)Mammalian TRIM36, which could play a regulatory role in exocytosis of the sperm vesicleMammalian tripartite, fibronectin type III and C-terminal B30.2/SPRY (TRIFIC)Mammalian muscle-specific RING finger (MURF) family. MURF proteins have an ability to form both homo- and heterodimers with each other and to associate with the microtubule cytoskeletonIn addition to RBCC, the COS domain is also found in association with B30.2/SPRY or fibronectin type-III (FN3) domains.The COS domain is predicted to consist of two α-helical coils [].
The C-CAP/cofactor C-like domain is present in several cytoskeleton-related proteins, which also contain a number of additional domains [, , , ]:Eukaryotic cyclase-associated protein (CAP or SRV2), a modular actin monomer binding that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localisation and the establishment of cell polarity.Vertebrate retinitis pigmentosa 2 (XRP2). In Homo sapiens (Human), it is the protein responsible for X-linked forms of retinitis pigmentosa, a disease characterised by severe retinal degeneration.Eukaryotic tubulin-specific chaperone cofactor C (TBCC), a GTPase- activating component of the tubulin-folding supercomplex, which directs the assembly of the alpha- and beta-tubulin heterodimer.The cyclase-associated protein C-CAP/cofactor C-like domain binds G-actin and is responsible for oligomerisation of the entire CAP molecule [], whereas the XRP2 C-CAP/cofactor C-like domain is required for binding of ADP ribosylation factor-like protein 3 (Arl3) [].The central core of the C-CAP/cofactor C-like domain is composed of six coils of right-handed parallel β-helices, termed coils 1-6, which form an elliptical barrel with a tightly packed interior. Each β-helical coil is composed of three relatively short β-strands, designated a-c, separated by sharp turns. Flanking the central β-helical core is an N-terminal β-strand, β0, that packs antiparallel to the core, and strand β7 packs antiparallel to the core near the C-terminal end of the parallel β-helix [, ].
This entry represents the microtubule-associated protein RP/EB (MAPRE) family, including MAPRE1 (EB1), MAPRE2 (RP1, also known as EB2), MAPRE3 (EBF3, also known as EB3) and their homologues from eukaryotes. Despite their high protein sequence conservation, the individual EBs exhibit different regulatory and functional properties []. For instance, EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes [].EB1 contains an N-terminal calponin homology (CH) domain that is responsible for the interaction with microtubules (MTs), and a C-terminal coiled coil domain that extends into a four-helix bundle, required for dimer formation []. Through their C-terminal sequences, EBs interact with most other known +TIPs (plus end tracking proteins) and recruit many of them to the growing MT ends [, ]. EB1 is involved in MT anchoring at the centrosome and cell migration []. EB2 is highly expressed in pancreatic cancer cells, and seems to be involved in perineural invasion []. EB3 is specifically upregulated upon myogenic differentiation. Knockdown of EB3, but not that of EB1, prevents myoblast elongation and fusion into myotubes []. This entry also includes bZIP transcription factor hapX from the yeast Neosartorya fumigata, which is a transcription factor required for repression of genes during iron starvation [].
Scavenger receptors type I and II were the first scavenger receptors purified and are products of alternative splicing of a single gene. They are now named as class A, type I and type II (SR-AI/II) or collectively SR-A member 1. They can recognise a wide variety of ligands, from bacteria and yeast to self (native proteins) and self-modified ligands and they are involved in host defense, homeostasis, antigen presentation, pathogenesis of neurodegenerative disorders and atherosclerosis [, ]. The type I and type II human scavenger receptors are similar to their bovine, rabbit and murine counterparts. They consist of 6 domains: cytoplasmic (I); membrane-spanning (II); spacer (III); α-helical coiled-coil (IV); collagen-like (V); and a type-specific C-terminal (VI) []. Immunohistochemical studies have indicated the presence of scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of these receptors in atherogenesis [].The macrophage scavenger receptor is trimeric and has unusual ligand-binding properties []. The trimeric structure of the bovine type I scavenger receptor contains 3 extracellular C-terminal cysteine-rich domains connected to the transmembrane domain by a long fibrous stalk. The stalk structure, which consists of an α-helical coiled coil and a collagen-like triple helix, has not previously been observed in an integral membrane protein [].
It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation [, ].The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the cell-cycle-regulated cohesion of microtubule-organizing centres. This 281kDa protein consists mainly of domains predicted to form coiled coil structures. The C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes []. During interphase, C-Nap1 localizes to the proximal ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis []. The structure of NAP-1 has a long α-helix, responsible for homodimerization via a previously uncharacterized antiparallel non-coiled-coil, and an alpha/beta domain composed of four-stranded antiparallel β-sheet, implicated in protein-protein interaction [].
This family represents ScpA, which along with ScpB () interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation [, ]. The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli [], where MukB () is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE () or MukF (), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions. In general scpA and scpB form an operon in most bacterial genomes. Flanking genes are highly variable suggesting that the operon has moved throughout evolution. Bacteria containing an smc gene also contain scpA or scpB but not necessarily both. An exception is found in Deinococcus radiodurans, which contains scpB but neither smc nor scpA. In the archaea the gene order SMC-ScpA is conserved in nearly all species, as is the very short distance between the two genes, indicating co-transcription of the both in different archaeal genera and arguing that interaction of the gene products is not confined to the homologues in Bacillus subtilis. It would seem probable that, in light of all the studies, SMC, ScpA and ScpB proteins or homologues act together in chromosome condensation and segregation in all prokaryotes [].
The exact function of the Hepatitis C non-structural 5A (NS5A) protein is not known, but it is an active component of the replicase, regulates replication and modulates a range of cellular processes including innate immunity and dysregulated cell growth. NS5A is organised into three domains, labelled I, II and III. Domain I contains a zinc-binding motif and an amphipathic N-terminal helix which promotes membrane association. Mutations disrupting either the membrane anchor or zinc binding are lethal for RNA replication [, ].This entry represents the 1b domain of NS5A. It consists of two distinct anti-parallel β-sheets surrounded by extensive random coil structures []. This domain contains a disulphide bond near its C-terminal not required for the RNA replicase functions of NS5A. The presence of the cited sulphide bond suggests that it is likely responsible of the structural arrangement of domains II and III, thus playing a regulatory role in NS5A function by serving as a conformation switch to modulate functions of NS5A in and out of the replicase [].
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily includes the middle finger domain, which is a seven-stranded, antiparallel, skewed β-roll with one α-helix [].
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily represents the N-terminal domain of Gp11, which has an α-helical structure that assumes an orthogonal bundle topology.
HR1 was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN) []. The first two of these repeats were later shownto bind the small G protein rho [, ]known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. This domain contains two long alpha helices forming a left-handed antiparallel coiled-coil fold termed the antiparallel coiled- coil (ACC) finger domain. The two long helices encompass the basic region and the leucine repeat region, which are identified as the Rho-binding region [, , ].This entry also includes Transducer of Cdc42-dependent actin assembly protein (TOCA) family proteins which contains a central HR1 (also known as Rho effector motif class 1, REM-1) which is closely related to Cdc42-interacting protein 4 (CIP4), effectors of the Rho family small G protein Cdc2 [].
TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response [, , ]. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair []. It also regulates CHD3 nucleosome remodelling during the DNA double-strand break (DSB) response []. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response []. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription []. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase []. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization []. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity [, ].
Ferredoxin-NADP(+) oxydoreductase (FNR) () transfers electrons from ferredoxin (or flavodoxin) to NADP(+) to generate NADPH. In eucaryotes, the nuclear-encoded, chloroplast-targeted enzyme contains two domains: an FAD-binding domain (see ) and an NADP(+)-binding domain. With the exception of Gloeobacter violaceus PCC 7421, the predicted sequences of all cyanobacterial petH genes, encoding FNR, correspond to a protein containing three domains. Two domains at the C terminus correspond to the FAD- and NADP(+)-binding domains of higher plants FNR protein, which compose the catalytic domains of the enzyme. The N-terminal domain is similar to phycobilisome (PBS)-associated linker proteins from numerous cyanobacteria [, , ]and is associated with:- CpcD, the phycocyanin (PC)-associated, rod-capping, linker polypeptide of PBS. The similarity spans nearly the entire sequence of this linker class.- CpcC, the PC-associated rod linker polypeptide. The similarity is confined only to the C terminus of this linker class.- ApcC, the allophycocyanin (APC)-associated, core linker polypeptide. The similarity only correspond to about half of the molecule.The CpcD-like domain has an elongated shape and consists of a three-strandedβ-sheet, two α-helices, one of which has only about one turn, and theconnecting random coil segments [].
(Bovine immunodeficiency virus) (BIV), like the human immunodeficiency virus, is a lentivirus. It shows a great deal of genomic diversity, mostly in the viral envelope gene []. This property of the BIV group of viruses may play an important role in the pathobiology of the virus, particularly the conserved (C) 2, hypervariable (V) 1, V2 and C3 regions [].The surface protein (SU) attaches the virus to the host cell by binding to its receptor. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusogenic potential by unmasking its fusion peptide. Fusion occurs at the host cell plasma membrane.The transmembrane protein (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm.
RPGR-interacting protein 1 (RPGRIP1) is mutated in the eye disease Leber congenital amaurosis (LCA) and its structural homologue, RPGRIP1-like (RPGRIP1L, also called NPHP8 or fantom), is mutated in many different ciliopathies [, ]. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR) []. Both consist of an N-terminal coiled coil domain, two C2 domains (C2N and C2C), and a C-terminal RPGR-interacting domain (RID). RID is a C2 domain with a canonical beta sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module [].Both RPGRIP1 and RPGRIP1L interact with the ciliary transition zone protein nephrocystin 4 (NPHP4) via their C2C domain [, ]. An hypothesis is that RPGRIP1 and RPGRIP1L function as cilium-specific scaffolds that recruit a Nek4 signaling network which regulates cilium stability []. The expression of RPGRIP1 seems to be limited to photoreceptors and amacrine cells in the retina [], whereas RPGRIP1L is found in other tissues as well.
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily represents the C-terminal domain of Gp11.
This entry represents the laminin-type EGF-like domain (LE) found in Laminin subunit gamma-1 and Netrin-1 from Homo sapiens and Mus musculus. Laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation [, ]. They are composed of distinct but related alpha, beta and gamma chains that form a cross-shaped molecule consisting of a long arm and three short globular arms. The long arm has a coiled coil structure contributed by all three chains and cross-linked by interchain disulphide bonds [, ]. Beside the different types of globular domains each subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines []. The tertiary structure of this domain is remotely similar in its N-terminal to that of the EGF-like module [, ](see ). The number of copies of the LE domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found.A schematic representation of the topology of the four disulphide bonds in the LE domain is shown below.+-------------------++-|-----------+ | +--------+ +-----------------+| | | | | | | |xxCxCxxxxxxxxxxxCxxxxxxxCxxCxxxxxGxxCxxCxxgaagxxxxxxxxxxxCxxsssssssssssssssssssssssssssssssssss'C': conserved cysteine involved in a disulphide bond'a': conserved aromatic residue'G': conserved glycine (lower case = less conserved)'s': region similar to the EGF-like domainLong consecutive arrays of LE domains in laminins form rod-like elements of limited flexibility [], which determine the spacing in the formation of laminin networks of basement membranes [].Netrins control guidance of the central nervous system commissural axons and peripheral motor axons [, , , ]. This protein also serves as a survival factor via its association with its receptors which prevent the initiation of apoptosis, thus being involved in tumorigenesis [, ].
Haemagglutinin (HA) is one of two main surface fusion glycoproteins embedded in the envelope of influenza viruses, the other being neuraminidase (NA). There are sixteen known HA subtypes (H1-H16) and nine NA subtypes (N1-N9), which together are used to classify influenza viruses (e.g. H5N1). The antigenic variations in HA and NA enable the virus to evade host antibodies made to previous influenza strains, accounting for recurrent influenza epidemics []. The HA glycoprotein is present in the viral membrane as a single polypeptide (HA0), which must be cleaved by the host's trypsin-like proteases to produce two peptides (HA1 and HA2) in order for the virus to be infectious. Once HA0 is cleaved, the newly exposed N-terminal of the HA2 peptide then acts to fuse the viral envelope to the cellular membrane of the host cell, which allows the viral negative-stranded RNA to infect the host cell. The type of host protease can influence the infectivity and pathogenicity of the virus.The haemagglutinin glycoprotein is a trimer containing three structurally distinct regions: a globular head consisting of anti-parallel β-sheets that form a β-sandwich with a jelly-roll fold (contains the receptor binding site and the HA1/HA2 cleavage site); a triple-stranded, coiled-coil, α-helical stalk; and a globular foot composed of anti-parallel β-sheets [, ]. Each monomer consists of an intact HA0 polypeptide with the HA1 and HA2 regions linked by disulphide bonds. The N terminus of HA1 provides the central strand in the 5-stranded globular foot, while the rest of the HA1 chain makes its way to the 8-stranded globular head. HA2 provides two alpha helices, which form part of the triple-stranded coiled-coil that stabilises the trimer, its C terminus providing the remaining strands of the 5-stranded globular foot.This entry represents the stalk segment of haemagglutinin in influenza C virus. It forms a coiled coil structure [].
Many microorganisms, such as methanogenic, acetogenic, nitrogen-fixing, photosynthetic, or sulphate-reducing bacteria, metabolise hydrogen. Hydrogen activation is mediated by a family of enzymes, termed hydrogenases, which either provide these organisms with reducing power from hydrogen oxidation, or act as electron sinks. There are two hydrogenases families that differ functionally from each other: NiFe hydrogenases tend to be more involved in hydrogen oxidation, while Iron-only FeFe (Fe only) hydrogenases in hydrogen production. Fe only hydrogenases () show a common core structure, which contains a moiety, deeply buried inside the protein, with an Fe-Fe dinuclear centre, nonproteic bridging, terminal CO and CN- ligands attached to each of the iron atoms, and a dithio moiety, which also bridges the two iron atoms and has been tentatively assigned as a di(thiomethyl)amine. This common core also harbours three [4Fe-4S]iron-sulphur clusters []. In FeFe hydrogenases, as in NiFe hydrogenases, the set of iron-sulphur clusters is dispersed regularly between the dinuclear Fe-Fe centre and the molecular surface. These clusters are distant by about 1.2 nm from each other but the [4Fe-4S]cluster closest to the dinuclear centre is covalently bound to one of the iron atoms though a thiolate bridging ligand. The moiety including the dinuclear centre, the thiolate bridging ligand, and the proximal [4Fe-4S]cluster is known as the H-cluster. A channel, lined with hydrophobic amino acid side chains, nearly connects the dinuclear centre and the molecular surface. Furthermore hydrogen-bonded water molecule sites have been identified at the interior and at the surface of the protein.The small subunit is comprised of alternating random coil and alpha helical structures that encompass the large subunit in a novel protein fold [].The localisation of iron hydrogenases can be cytoplasmic or periplasmic. Periplasmic iron hydrogenases in Desulfovibrio consists of a large subunit (HydA) and a small subunit (HydB) [].
This family is specific for E proteins from alphacoronaviruses.E protein is the smallest of the major structural proteins. It is conserved among Coronavirus strains. It is an integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis []. During the replication cycle, E is abundantly expressed inside the infected cell, but only a small portion is incorporated into the virus envelope. The majority of the protein participates in viral assembly and budding [, ]. It can act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport [, ]. Additionally, the E protein is thought to prevent M protein aggregation and induce membrane curvature [].SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, which leads to the overproduction of IL-1beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway and interacts with the cellular protein syntenin, triggering p38 MARK activation. These signalling cascades result in exacerbated inflammation and immunopathology [].Cov E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C terminus, which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic α-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins have been proposed to have at least two roles. One is related to their TM channel domain. This would be active in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficient trafficking of virions. The other would be related to their extramembranedomains, particularly the C-terminal domain. This is involved in protein-protein interactions and targeting, among other roles [, , , ]. In the CoV E protein structure a longer α-helix encompasses the TM domain, which is connected to another shorter C-terminal α-helix by a flexible linker domain, forming an L-shape [Li]. The CoV E pentamer is a right handed α-helical bundle where the C-terminal tails coil around each other [].
E protein is the smallest of the major structural proteins. It is conserved among Coronavirus strains. It is an integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis []. During the replication cycle, E is abundantly expressed inside the infected cell, but only a small portion is incorporated into the virus envelope. The majority of the protein participates in viral assembly and budding [, ]. It can act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport [, ]. Additionally, the E protein is thought to prevent M protein aggregation and induce membrane curvature [].SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, which leads to the overproduction of IL-1beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway and interacts with the cellular protein syntenin, triggering p38 MARK activation. These signalling cascades result in exacerbated inflammation and immunopathology [].Cov E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C terminus, which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic α-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins have been proposed to have at least two roles. One is related to their TM channel domain. This would be active in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficient trafficking of virions. The other would be related to their extramembrane domains, particularly the C-terminal domain. This is involved in protein-protein interactions and targeting, among other roles [, , , ]. In the CoV E protein structure a longer α-helix encompasses the TM domain, which is connected to another shorter C-terminal α-helix by a flexible linker domain, forming an L-shape [Li]. The CoV E pentamer is a right handed α-helical bundle where the C-terminal tails coil around each other [].
This family is specific for E proteins from betacoronaviruses.E protein is the smallest of the major structural proteins. It is conserved among Coronavirus strains. It is an integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis []. During the replication cycle, E is abundantly expressed inside the infected cell, but only a small portion is incorporated into the virus envelope. The majority of the protein participates in viral assembly and budding [, ]. It can act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport [, ]. Additionally, the E protein is thought to prevent M protein aggregation and induce membrane curvature [].SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, which leads to the overproduction of IL-1beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway and interacts with the cellular protein syntenin, triggering p38 MARK activation. These signalling cascades result in exacerbated inflammation and immunopathology [].Cov E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C terminus, which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic α-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins have been proposed to have at least two roles. One is related to their TM channel domain. This would be active in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficient trafficking of virions. The other would be related to their extramembrane domains, particularly the C-terminal domain. This is involved in protein-protein interactions and targeting, among other roles [, , , ]. In the CoV E protein structure a longer α-helix encompasses the TM domain, which is connected to another shorter C-terminal α-helix by a flexible linker domain, forming an L-shape [Li]. The CoV E pentamer is a right handed α-helical bundle where the C-terminal tails coil around each other [].
This entry represents the Envelope (E) small membrane protein of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV) or COVID-19 virus.E protein is the smallest of the major structural proteins. It is conserved among Coronavirus strains. It is an integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis []. During the replication cycle, E is abundantly expressed inside the infected cell, but only a small portion is incorporated into the virus envelope. The majority of the protein participates in viral assembly and budding [, ]. It can act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport [, ]. Additionally, the E protein is thought to prevent M protein aggregation and induce membrane curvature [].SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, which leads to the overproduction of IL-1beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway and interacts with the cellular protein syntenin, triggering p38 MARK activation. These signalling cascades result in exacerbated inflammation and immunopathology [].Cov E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C terminus, which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic α-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins have been proposed to have at least two roles. One is related to their TM channel domain. This would be active in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficient trafficking of virions. The other would be related to their extramembrane domains, particularly the C-terminal domain. This is involved in protein-protein interactions and targeting, among other roles [, , , ]. In the CoV E protein structure a longer α-helix encompasses the TM domain, which is connected to another shorter C-terminal α-helix by a flexible linker domain, forming an L-shape [Li]. The CoV E pentamer is a right handed α-helical bundle where the C-terminal tails coil around each other [].
This entry represents the Envelope (E) small membrane protein of Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as E proteins from related coronaviruses.E protein is the smallest of the major structural proteins. It is conserved among Coronavirus strains. It is an integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis []. During the replication cycle, E is abundantly expressed inside the infected cell, but only a small portion is incorporated into the virus envelope. The majority of the protein participates in viral assembly and budding [, ]. It can act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport [, ]. Additionally, the E protein is thought to prevent M protein aggregation and induce membrane curvature [].SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, which leads to the overproduction of IL-1beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway and interacts with the cellular protein syntenin, triggering p38 MARK activation. These signalling cascades result in exacerbated inflammation and immunopathology [].Cov E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C terminus, which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic α-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins have been proposed to have at least two roles. One is related to their TM channel domain. This would be active in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficienttrafficking of virions. The other would be related to their extramembrane domains, particularly the C-terminal domain. This is involved in protein-protein interactions and targeting, among other roles [, , , ]. In the CoV E protein structure a longer α-helix encompasses the TM domain, which is connected to another shorter C-terminal α-helix by a flexible linker domain, forming an L-shape [Li]. The CoV E pentamer is a right handed α-helical bundle where the C-terminal tails coil around each other [].
This entry represents the C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), also known as CD209 antigen, and the related receptor, DC-SIGN receptor (DC-SIGNR), also known as CD209 antigen-like protein 1 or C-type lectin domain family 4 member M. This group also contains proteins similar to hepatic asialoglycoprotein receptor (ASGP-R) and langerin (also known as CD207 or C-type lectin domain family 4 member K) in human. These proteins are type II membrane proteins with a CTLD ectodomain. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins [].DC-SIGN is thought to mediate the initial contact between dendritic cells and resting T cells, and may also mediate the rolling of DCs on epithelium []. DC-SIGN and DC-SIGNR bind to oligosaccharides present on human tissues, as well as on pathogens including parasites, bacteria, and viruses. DC-SIGN and DC-SIGNR bind to HIV, enhancing viral infection of T cells []. DC-SIGN and DC-SIGNR are homotetrameric, and contain four CTLDs stabilized by a coiled coil of alpha helices []. The hepatic ASGP-R is an endocytic recycling receptor which binds and internalizes desialylated glycoproteins having a terminal galactose or N-acetylgalactosamine residues on their N-linked carbohydrate chains, via the clathrin-coated pit mediated endocytic pathway, and delivers them to lysosomes for degradation. It has been proposed that glycoproteins bearing terminals 'Sia (sialic acid) alpha2, 6GalNAc' and 'Sia alpha2, 6Gal' are endogenous ligands for ASGP-R, and that ASGP-R participates in regulating the relative concentration of serum glycoproteins bearing alpha 2,6-linked Sia []. The human ASGP-R is a hetero-oligomer composed of two subunits, both of which are found within this group []. Langerin is expressed in a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin induces the formation of Birbeck Granules (BGs) and associates with these BGs following internalization []. Langerin binds, in a calcium-dependent manner, to glyco-conjugates containing mannose and related sugars mediating their uptake and degradation. Langerin molecules oligomerize as trimers with three CTLDs held together by a coiled-coil of alpha helices [].
This entry represents the C-lobe of FERM domain found in the ERM family members, including ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain, a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor [, ]. The ERM proteins exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin [, ]. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [, ].
The Krueppel-associated box (KRAB) is a domain of around 75 amino acids that is found in the N-terminal part of about one third of eukaryotic Krueppel-type C2H2 zinc finger proteins (ZFPs) []. It is enriched in charged amino acids and can be divided into subregions A and B, which are predicted to fold into two amphipathic α-helices. The KRAB A and B boxes can be separated by variable spacer segments and many KRAB proteins contain only the A box [].The functions currently known for members of the KRAB-containing protein family include transcriptional repression of RNA polymerase I, II and III promoters, binding and splicing of RNA, and control of nucleolus function. The KRAB domain functions as a transcriptional repressor when tethered to the template DNA by a DNA-binding domain. A sequence of 45 amino acids in the KRAB A subdomain has been shown to be necessary and sufficient for transcriptional repression. The B box does not repress by itself but does potentiate the repression exerted by the KRAB A subdomain [, ]. Gene silencing requires the binding of the KRAB domain to the RING-B box-coiled coil (RBCC) domain of the KAP-1/TIF1-beta corepressor. As KAP-1 binds to the heterochromatin proteins HP1, it has been proposed that the KRAB-ZFP-bound target gene could be silenced following recruitment to heterochromatin [, ].KRAB-ZFPs probably constitute the single largest class of transcription factors within the human genome []. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B. Although the function of KRAB-ZFPs is largely unknown, they appear to play important roles during cell differentiation and development. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta, KRAB-A interacting protein and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation [].
The SMC (structural maintenance of chromosomes) family of proteins, exist in virtually all organisms, including bacteria and archaea. The SMC proteins are essential for successful chromosome transmission during replication and segregation of the genome in all organisms. They function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression [, ].SMCs are generally present as single proteins in bacteria, and as at least six distinct proteins in eukaryotes. The proteins range in size from approximately 110 to 170kDa, and share a five-domain structure, with globular N- and C-terminal domains separated by a long(circa 100 nm or 900 residues) coiled coil segment in the centre of which is a globular ''hinge'' domain, characterised by a set of four highly conserved glycine residuesthat are typical of flexible regionsin a protein. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T), which has been shown by mutational studies to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif (XXXXD, where X is any hydrophobic residue), and a LSGG motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases []. All SMC proteins appear to form dimers, either forming homodimers, as in the case of prokaryotic SMC proteins, or heterodimers between different but related SMC proteins. The dimers form core components of large multiprotein complexes. The best known complexes are cohesin, which is responsible for sister-chromatid cohesion, and condensin, which is required for full chromosome condensation in mitosis. SMC dimers are arranged in an antiparallel alignment. This orientation brings the N- and C-terminal globular domains (from either different or identical protamers) together, which unites an ATP binding site (Walker A motif) within the N-terminal domain with a Walker B motif (DA box) within the C-terminal domain, to form a potentially functional ATPase. Protein interaction and microscopy data suggest that SMC dimers form a ring-like structure which might embrace DNA molecules. Non-SMC subunits associate with the SMC amino- and carboxy-terminal domains.Proteins in this entry include SMC1/2/3/4 from Saccharomyces cerevisiae. SMC1-SMC3 heterodimer is part of the cohesin complex, which is required for sister chromatid cohesion in mitosis and meiosis []. SMC2-SMC4 heterodimer is part of the condensin complex, which is required for chromosome condensation during both mitosis and meiosis [, ].
The SMC (structural maintenance of chromosomes) family of proteins, exist in virtually all organisms, including bacteria and archaea. The SMC proteins are essential for successful chromosome transmission during replication and segregation of the genome in all organisms. They function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression [].SMCs are generally present as single proteins in bacteria, and as at least six distinct proteins in eukaryotes. The proteins range in size from approximately 110 to 170kDa, and share a five-domain structure, with globular N- and C-terminal domains separated by a long(circa 100 nm or 900 residues) coiled coil segment in the centre of which is a globular ''hinge'' domain, characterised by a set of four highly conserved glycine residuesthat are typical of flexible regions in a protein. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T), which has been shown by mutational studies to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif (XXXXD, where X is any hydrophobic residue), and a LSGG motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases []. All SMC proteins appear to form dimers, either forming homodimers, as in the case of prokaryotic SMC proteins, or heterodimers between different but related SMC proteins. The dimers form core components of large multiprotein complexes. The best known complexes are cohesin, which is responsible for sister-chromatid cohesion, and condensin, which is required for full chromosome condensation in mitosis. SMC dimers are arranged in an antiparallel alignment. This orientation brings the N- and C-terminal globular domains (from either different or identical protamers) together, which unites an ATP binding site (Walker A motif) within the N-terminal domain with a Walker B motif (DA box) within the C-terminal domain, to form a potentially functional ATPase. Protein interaction and microscopy data suggest that SMC dimers form a ring-like structure which might embrace DNA molecules. Non-SMC subunits associate with the SMC amino- and carboxy-terminal domains.This entry represents the SMC protein from bacteria and archaea [, , ].
The Krueppel-associated box (KRAB) is a domain of around 75 amino acids that is found in the N-terminal part of about one third of eukaryotic Krueppel-type C2H2 zinc finger proteins (ZFPs) []. It is enriched in charged amino acids and can be divided into subregions A and B, which are predicted to fold into two amphipathic α-helices. The KRAB A and B boxes can be separated by variable spacer segments and many KRAB proteins contain only the A box [].The functions currently known for members of the KRAB-containing protein family include transcriptional repression of RNA polymerase I, II and III promoters, binding and splicing of RNA, and control of nucleolus function. The KRAB domain functions as a transcriptional repressor when tethered to the template DNA by a DNA-binding domain. A sequence of 45 amino acids in the KRAB A subdomain has been shown to be necessary and sufficient for transcriptional repression. The B box does not repress by itself but does potentiate the repression exerted by the KRAB A subdomain [, ]. Gene silencing requires the binding of the KRAB domain to the RING-B box-coiled coil (RBCC) domain of the KAP-1/TIF1-beta corepressor. As KAP-1 binds to the heterochromatin proteins HP1, it has been proposed that the KRAB-ZFP-bound target gene could be silenced following recruitment to heterochromatin [, ].KRAB-ZFPs probably constitute the single largest class of transcription factors within the human genome []. The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B. Although the function of KRAB-ZFPs is largely unknown, they appear to play important roles during cell differentiation and development. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta, KRAB-A interacting protein and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation [].
Kinesin [, , ]is a microtubule-associated force-producing protein that may play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.The heavy chain is composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it is known to hydrolyse ATP, to bind and move on microtubules), a central α-helical coiled coil domain that mediates the heavy chain dimerisation; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.The kinesin motor domain comprises five motifs, namely N1 (P-loop), N2 (Switch I), N3 (Switch II), N4 and L2 (KVD finger) []. It has a mixed eight stranded β-sheet core with flanking solvent exposed α-helices and a small three-stranded antiparallel β-sheet in the N-terminal region [].A number of proteins have been recently found that contain a domain similar to that of the kinesin 'motor' domain [, ]:Drosophila melanogaster claret segregational protein (ncd). Ncd is required for normal chromosomal segregation in meiosis, in females, and in early mitotic divisions of the embryo. The ncd motor activity is directed toward the microtubule's minus end.Homo sapiens CENP-E []. CENP-E is a protein that associates with kinetochores during chromosome congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is probably an important motor molecule in chromosome movement and/or spindle elongation.H. sapiens mitotic kinesin-like protein-1 (MKLP-1), a motor protein whose activity is directed toward the microtubule's plus end.Saccharomyces cerevisiae KAR3 protein, which is essential for nuclear fusion during mating. KAR3 may mediate microtubule sliding during nuclear fusion and possibly mitosis.S. cerevisiae CIN8 and KIP1 proteins which are required for the assembly of the mitotic spindle. Both proteins seem to interact with spindle microtubules to produce anoutwardly directed force acting upon the poles.Emericella nidulans (Aspergillus nidulans) bimC, which plays an important role in nuclear division.A. nidulans klpA.Caenorhabditis elegans unc-104, which may be required for the transport of substances needed for neuronal cell differentiation.C. elegans osm-3.Xenopus laevis Eg5, which may be involved in mitosis.Arabidopsis thaliana KatA, KatB and katC.Chlamydomonas reinhardtii FLA10/KHP1 and KLP1. Both proteins seem to play a role in the rotation or twisting of the microtubules of the flagella.C. elegans hypothetical protein T09A5.2.The kinesin motor domain is located in the N-terminal part of most of the above proteins, with the exception of KAR3, klpA, and ncd where it is located in the C-terminal section.The kinesin motor domain contains about 330 amino acids. An ATP-binding motif of type A is found near position 80 to 90, the C-terminal half of the domain is involved in microtubule-binding.Interestingly, kinesin motor domain has a striking structural similarity to the core of the catalytic domain of the actin-based motor myosin [].
Methyl transfer from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalysed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects ofthe role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.Three classes of DNA Mtases transfer the methyl group from AdoMet to the target base to form either N-6-methyladenine, or N-4-methylcytosine, or C-5- methylcytosine. In C-5-cytosine Mtases, ten conserved motifs are arranged in the same order []. Motif I (a glycine-rich or closely related consensus sequence; FAGxGG in M.HhaI []), shared by other AdoMet-Mtases [], is part of the cofactor binding site and motif IV (PCQ) is part of the catalytic site. In contrast, sequence comparison among N-6-adenine and N-4-cytosine Mtases indicated two of the conserved segments [], although more conserved segments may be present. One of them corresponds to motif I in C-5-cytosine Mtases, and the other is named (D/N/S)PP(Y/F). Crystal structures are known for a number of Mtases [, , , ]. The cofactor binding sites are almost identical and the essential catalytic amino acids coincide. The comparable protein folding and the existence of equivalent amino acids in similar secondary and tertiary positions indicate that many (if not all) AdoMet-Mtases have a common catalytic domain structure. This permits tertiary structure prediction of other DNA, RNA, protein, and small-molecule AdoMet-Mtases from their amino acid sequences [].CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region [].CheR proteins are part of the chemotaxis signaling mechanism which methylates the chemotaxis receptor at specific glutamate residues. This entry refers to the C-terminal SAM-binding domain of the CherR-type MCP methyltransferases, which are found in bacteria, archaea and green plants. This entry is found in association with .
Kinesin [, , ]is a microtubule-associated force-producing protein that may play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.The heavy chain is composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it is known to hydrolyse ATP, to bind and move on microtubules), a central α-helical coiled coil domain that mediates the heavy chain dimerisation; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.The kinesin motor domain comprises five motifs, namely N1 (P-loop), N2 (Switch I), N3 (Switch II), N4 and L2 (KVD finger) []. It has a mixed eight stranded β-sheet core with flanking solvent exposed α-helices and a small three-stranded antiparallel β-sheet in the N-terminal region [].A number of proteins have been recently found that contain a domain similar to that of the kinesin 'motor' domain [, ]:Drosophila melanogaster claret segregational protein (ncd). Ncd is required for normal chromosomal segregation in meiosis, in females, and in early mitotic divisions of the embryo. The ncd motor activity is directed toward the microtubule's minus end.Homo sapiens CENP-E []. CENP-E is a protein that associates with kinetochores during chromosome congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is probably an important motor molecule in chromosome movement and/or spindle elongation.H. sapiens mitotic kinesin-like protein-1 (MKLP-1), a motor protein whose activity is directed toward the microtubule's plus end.Saccharomyces cerevisiae KAR3 protein, which is essential for nuclear fusion during mating. KAR3 may mediate microtubule sliding during nuclear fusion and possibly mitosis.S. cerevisiae CIN8 and KIP1 proteins which are required for the assembly of the mitotic spindle. Both proteins seem to interact with spindle microtubules to produce an outwardly directed force acting upon the poles.Emericella nidulans (Aspergillus nidulans) bimC, which plays an important role in nuclear division.A. nidulans klpA.Caenorhabditis elegans unc-104, which may be required for the transport of substances needed for neuronal cell differentiation.C. elegans osm-3.Xenopus laevis Eg5, which may be involved in mitosis.Arabidopsis thaliana KatA, KatB and katC.Chlamydomonas reinhardtii FLA10/KHP1 and KLP1. Both proteins seem to play a role in the rotation or twisting of the microtubules of the flagella.C. elegans hypothetical protein T09A5.2.The kinesin motor domain is located in the N-terminal part of most of the above proteins, with the exception of KAR3, klpA, and ncd where it is located in the C-terminal section.The kinesin motor domain contains about 330 amino acids. An ATP-binding motif of type A is found near position 80 to 90, the C-terminal half of the domain is involved in microtubule-binding.The signature pattern for this entry is derived from a conserved decapeptide inside the microtubule-binding region.
Kinesin [, , ]is a microtubule-associated force-producing protein that may play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.The heavy chain is composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it is known to hydrolyse ATP, to bind and move on microtubules), a central α-helical coiled coil domain that mediates the heavy chain dimerisation; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.The kinesin motor domain comprises five motifs, namely N1 (P-loop), N2 (Switch I), N3 (Switch II), N4 and L2 (KVD finger) []. It has a mixed eight stranded β-sheet core with flanking solvent exposed α-helices and a small three-stranded antiparallel β-sheet in the N-terminal region [].A number of proteins have been recently found that contain a domain similar to that of the kinesin 'motor' domain [, ]:Drosophila melanogaster claret segregational protein (ncd). Ncd is required for normal chromosomal segregation in meiosis, in females, and in early mitotic divisions of the embryo. The ncd motor activity is directed toward the microtubule's minus end.Homo sapiens CENP-E []. CENP-E is a protein that associates with kinetochores during chromosome congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is probably an important motor molecule in chromosome movement and/or spindle elongation.H. sapiens mitotic kinesin-like protein-1 (MKLP-1), a motor protein whose activity is directed toward the microtubule's plus end.Saccharomyces cerevisiae KAR3 protein, which is essential for nuclear fusion during mating. KAR3 may mediatemicrotubule sliding during nuclear fusion and possibly mitosis.S. cerevisiae CIN8 and KIP1 proteins which are required for the assembly of the mitotic spindle. Both proteins seem to interact with spindle microtubules to produce an outwardly directed force acting upon the poles.Emericella nidulans (Aspergillus nidulans) bimC, which plays an important role in nuclear division.A. nidulans klpA.Caenorhabditis elegans unc-104, which may be required for the transport of substances needed for neuronal cell differentiation.C. elegans osm-3.Xenopus laevis Eg5, which may be involved in mitosis.Arabidopsis thaliana KatA, KatB and katC.Chlamydomonas reinhardtii FLA10/KHP1 and KLP1. Both proteins seem to play a role in the rotation or twisting of the microtubules of the flagella.C. elegans hypothetical protein T09A5.2.The kinesin motor domain is located in the N-terminal part of most of the above proteins, with the exception of KAR3, klpA, and ncd where it is located in the C-terminal section.The kinesin motor domain contains about 330 amino acids. An ATP-binding motif of type A is found near position 80 to 90, the C-terminal half of the domain is involved in microtubule-binding.
