The osmosensory transporter coiled coil is a C-terminal domain found in various bacterial osmoprotective transporters, such as ProP, Proline/betaine transporter, Proline permease 2 and the citrate proton symporters. It adopts an antiparallel coiled-coil structure, and is essential for osmosensory and osmoprotectant transporter function [].
This entry represents the N-terminal coiled coil region of TSP-5, also known as cartilage oligomeric matrix protein (COMP). It forms a pentameric left-handed coiled coil (COMPcc) with a channel that is a unique carrier for lipophilic compounds []. It is known to bind hydrophilic signaling molecules such as vitamin D3 and vitamin A, making it a possible targeted drug delivery system []. TSP-5/COMP is expressed in all types of cartilage as well as in the vitreous of the eye, tendons, vascular smooth muscle cells, and heart. The pentamer is stabilized by inter-subunit disulfide bonds formed between cysteine residues adjacent to the C-terminal end of the coiled coil region []. TSP-5 is essential for modulating the phenotypic transition of vascular smooth muscle cells and vascular remodeling. Mutations in TSP-5 result in two different inherited chondrodysplasias and osteoarthritic phenotypes: pseudoachondroplasia and multiple epithelial dysplasia []. Deficiency of TSP-5 causes dilated cardiomyopathy (DCM), a common cause of congestive heart failure []. Early increase in serum TSP-5 is associated with joint damage progression in patients with rheumatoid arthritis, thus representing a novel indicator of an activated destructive process in the joint [].
This domain is predominantly found in the actin-bundling protein cortexillin I and II from Dictyostelium discoideum (Slime mold). The domain has a structure consisting of an 18-heptad-repeat α-helical coiled-coil, and is a prerequisite for the assembly of Cortexillin I [].
Tetrabrachion is a surface layer glycoprotein from the hyperthermophilic archaebacterium Staphylothermus marinus []. The tetrabrachion protein complex consists of four identical subunits that form an α-helical coiled coil stalk anchored to the cell membrane that branches into four arms. Two molecules of the subtilisin-like protease STABLE are noncovalently bound near the centre of the stalk. This entry represents the protease binding region of the tetrabrachion complex, for which a right-handed coiled coil structure has been proposed. The parallel right-handed coiled-coil tetramer is stabilized by a complex pattern of complementary hydrophobic interactions between neighbouring helices [].
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents a domain consisting of four long helices that forms a bundle with a left-handed twist (coiled coil), in a right-handed superhelix.
LINC complexes are formed by coupling of KASH (Klarsicht, ANC-1, and Syne/Nesprin Homology) and SUN (Sad1 and UNC-84) proteins from the inner and outer nuclear membranes (INM and ONM, respectively). The formation of LINC complexes by KASH and SUN proteins at the nuclear envelope (NE) establishes the physical linkage between the cytoskeleton and nuclear lamina, which is instrumental for the mechanical force transmission from the cytoplasm to the nuclear interior, and is essential for cellular processes such as nuclear positioning and migration, centrosome-nucleus anchorage, and chromosome dynamics. SUN2 possesses two coiled-coil domains (CC1 and CC2). These coiled-coil domains are also believed to act as rigid spacers to delineate the distance between the ONM and INM of the NE. Furthermore, the two coiled-coil domains of SUN2 have been indicated to be able to directly modulate SUN domain activity and regulate the subsequent interactions between the SUN and KASH domains. CC2 forms a three-helix bundle to lock the SUN domain in an inactive conformation acting as an inhibitory component. Structure-based sequence analysis demonstrated that several Gly residues are located in the flexible linker regions between the three helices which would ideally provide the breaks/turns in CC2 for three-helix bundle formation. The last helix alpha3 of CC2 (that is immediately connected to the SUN domain) has been shown to be an essential segment for promoting SUN domain trimerization in the SUN-KASH complex structure [, ].
The 380kDa motor unit of dynein belongs to the AAA class of chaperone-like ATPases. The core of the 380kDa motor unit contains a concatenated chain of six AAA modules (D1-6), of which four correspond to the ATP binding sites with P-loop signatures, and two are modules in which the P loop has been lost in evolution. This domain occurs between D4 and D5 and includes the two predicted α-helical coiled coil segments that form the stalk supporting the ATP-sensitive microtubule binding component [].
Fibrinogen plays key roles in both blood clotting and platelet aggregation. During blood clot formation, the conversion of soluble fibrinogen to insoluble fibrin is triggered by thrombin, resulting in the polymerisation of fibrin, which forms a soft clot; this is then converted to a hard clot by factor XIIIA, which cross-links fibrin molecules. Platelet aggregation involves the binding of the platelet protein receptor integrin alpha(IIb)-beta(3) to the C-terminal D domain of fibrinogen []. In addition to platelet aggregation, platelet-fibrinogen interaction mediates both adhesion and fibrin clot retraction. Fibrinogen occurs as a dimer, where each monomer is composed of three non-identical chains, alpha, beta and gamma, linked together by several disulphide bonds []. The N-terminals of all six chains come together to form the centre of the molecule (E domain), from which the monomers extend in opposite directions as coiled coils, followed by C-terminal globular domains (D domains). Therefore, the domain composition is: D-coil-E-coil-D. At each end, the C-terminal of the alpha chain extends beyond the D domain as a protuberance that is important for cross-linking the molecule. During clot formation, the N-terminal fragments of the alpha and beta chains (within the E domain) in fibrinogen are cleaved by thrombin, releasing fibrinopeptides A and B, respectively, and producing fibrin. This cleavage results in the exposure of four binding sites on the E domain, each of which can bind to a D domain from different fibrin molecules. The binding of fibrin molecules produces a polymer consisting of a lattice network of fibrins that form a long, branching, flexible fibre [, ]. Fibrin fibres interact with platelets to increase the size of the clot, as well as with several different proteins and cells, thereby promoting the inflammatory response and concentrating the cells required for wound repair at the site of damage.This entry represents the coiled-coil domain and part of the N-terminal E domain found in all three fibrinogen polypeptides, namely the alpha, beta and gamma chains.
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus []. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain () that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [, , ]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.This entry represents a domain found in Dictyostelium STAT proteins. This domain adopts a structure consisting of four long α-helices, folded into a coiled coil. It is responsible for nuclear export of the protein [].
Vasodilator-stimulated phosphoprotein (VASP) is an actin cytoskeletal regulatory protein. This superfamily corresponds to the tetramerisation domain which forms a right handed alpha helical coiled coil structure [].
Vasodilator-stimulated phosphoprotein (VASP) is an actin cytoskeletal regulatory protein. This region corresponds to the tetramerisation domain which forms a right handed alpha helical coiled coil structure [].
This is a family of unknown function mainly found in bacteria and archaea. A number of this family members have a coiled coil domain at their C terminus.
This superfamily represents the N-terminal coiled coil domain of the delta antigen from the hepatitis D virus (HDV). The hepatitis delta antigen dimerises through this anti-parallel coiled coil domain. Dimers then associate further to form octamers through residues in the coiled-coil domain and residues C-terminal to this domain. This domain may play a role in binding the viral RNA [].
Cytochrome c oxidase assembly factor 3, previously known as coiled coil domain-containing protein 56 (CCDC56), plays a critical role in the biogenesis and activity of cytochrome c oxidase (COX) [].
This is the coiled coil (CC) - marked box (MB) domain of E2F transcription factors. This domain forms a heterodimer with the corresponding domain of the DP transcription factor, the heterodimer binds the C terminus of retinoblastoma protein [].
Several proteins have been identified that localise to centrosomes and spindle poles, and they have been named accordingly to their molecular weight []. This entry represents a coiled coil domain found in centrosomal protein of 44kDa (CEP44).
This domain occurs at the N terminus of Rnk (regulator of nucleoside diphosphate kinase), an RNA polymerase-interacting protein of the GreA/GreB family []. It has a coiled coil structure [].
This family represents the small subunit of the Fe-only hydrogenases (). The subunit is comprised of alternating random coil and α-helical structures that encompasses the large subunit in a novel protein fold [].
The B-box C-terminal domain is a coiled coil region C-terminal to (some) B-Box domains. It is found in transcription intermediary factor 1-alpha, which associates with DNA-bound estrogen receptors; ring finger protein, a putative transcriptional regulator; and the GTP-binding protein Ard-1.
The structure of a representative of this family has been solved and found to form a tetrameric structure of prefoldin-like architecture with the β-barrel core and helical coiled coil tentacles. This suggests that this family may act as molecular chaperones.
Tetrabrachion forms a parallel right-handed coiled coil structure with hydrophobic interactions and salt bridges forming a thermostable tetrameric structure. It contains large hydrophobic cavities. No function is known for this family of proteins [].
Nischarin, also known as Imidazoline Receptor Antisera-Selected (IRAS), contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes []. IRAS has been shown to interact with integrin and inhibit cell migration []. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin [].This entry represents the PX domain of nischarin/IRAS.
The Yersinia adhesin A (YadA) is a trimeric autotransporter adhesin of enteric yersiniae. It consists of three major domains: a head mediating adherence to host cells, a stalk involved in serum resistance, and an anchor that forms a membrane pore and is responsible for the autotransport function [].This entry represents the head domain of YadA. This domain is composed almost solely of β-sheets making a novel nine coiled left-handed parallel β-roll (LPBR), surrounded by a partly disordered (N)-terminal random coil and a C-terminal neck region, which consists of a random coil and a short helix at the start of the stalk domain [].
The tertiary structures of pectate lyases andrhamnogalacturonase A show a stack of parallel betastrands that are coiled into a large helix. Each coil of the helix representsa structural repeat that, insome homologues, can be recognised from sequence information alone.Conservation ofasparagines might be connected with asparagine-ladders that contribute to thestability of the fold.Proteins containing these repeats most often are enzymes with polysaccharidesubstrates [].
This entry represents a coiled-coil domain found in cytochrome c oxidase assembly factor 3 and homologues.Cytochrome c oxidase assembly factor 3, previously known as coiled coil domain-containing protein 56 (CCDC56), plays a critical role in the biogenesis and activity of cytochrome c oxidase (COX) [].
This entry represents the conserved region of NUDE proteins. Proteins containing this domain are homologues of the nuclear distribution protein RO11 of Neurospora crassa. NUDE interacts with the NUDF via an N-terminal coiled coil domain; this is the only domain which is absolutely required for NUDE function.
Matrix (M) protein is an important structural component of rhabdovirus virions, and also plays a number of roles during the replication cycle of the virus []. It is involved in condensing and targeting the ribonucleoprotein (RNP) coil to the plasma membrane. M interacts specifically with the transmembrane spike protein (G) and it is important for the incorporation of G protein into budding virions [].
This entry represents the heptad repeat domain which is conserved at the C terminus of Fzo/mitofusion family of GTPases. Fzo is a mediator of mitochondrial fusion during spermatogenesis []. This conserved region is also found in the human mitofusin protein [].This domain forms a dimeric antiparallel coiled coil structure, which has been proposed to act as a mitochodrial tether before vesicle fusion [].
The Gp7 protein contains a DNA-binding function and may have a role in mediating the structural transition from prohead to mature virus and also scaffold release []. Gp7 is arranged within the capsid as a series of concentric shells [].The structure of Gp7 forms a dimer that resemble arrows, with a four-helix bundle composing the arrowhead and a coiled coil forming the tail [].
Family members are found in small bacterial proteins, and also in the heavy chains of fungal proteins that contain the domain kinesin, in which this region is located C-terminal of the motor domain. Members of this family may form coiled coil structures [].
Matrix (M) protein is an important structural component of rhabdovirus virions, and also plays a number of roles during the replication cycle of the virus []. It is involved in condensing and targeting the ribonucleoprotein (RNP) coil to the plasma membrane. M interacts specifically with the transmembrane spike protein (G) and it is important for the incorporation of G protein into budding virions [].
This entry represents a short domain found the matrilin (cartilage matrix) proteins. It forms a coiled coil structure and contains a single cysteine residue at its start which is likely to form a di-sulphide bridge with a corresponding cysteine in an upstream EGF domain, thereby spanning the VWA domain of the protein ().This domain is likely to be responsible for protein trimerisation [, ].
The osmosensory transporter coiled coil is a C-terminal domain found in various bacterial osmoprotective transporters, such as ProP, Proline/betaine transporter, Proline permease 2 and the citrate proton symporters. It adopts an antiparallel coiled-coil structure, and is essential for osmosensory and osmoprotectant transporter function [].
This mitochondrial matrix protein superfamily contains members of the MAM33 superfamily which bind to the globular 'heads' of C1Q.b. It is thought to be involved in mitochondrial oxidative phosphorylation and in nucleus-mitochondrion interactions [, , ]. Its structure consists of an beta(7)-alpha(2) fold with N- and C-terminal extensions forming a coiled coil subdomain.
Family members are found in small bacterial proteins, and also in the heavy chains of fungal proteins that contain the domain kinesin, in which this region is located C-terminal of the motor domain. Members of this family may form coiled coil structures [].
This entry represents a short domain found the matrilin (cartilage matrix) proteins. It forms a coiled coil structure and contains a single cysteine residue at its start which is likely to form a di-sulphide bridge with a corresponding cysteine in an upstream EGF domain, thereby spanning the VWA domain of the protein ().This domain is likely to be responsible for protein trimerisation [, ].
The E2F transcription factors associated with the corresponding domain of the DP transcription factor forming an heterodimer fold with the N-terminal long helices of both chains forming a parallel coiled coil and their C-terminal folded β-hairpins interlocking together in a β-sandwich. This complex binds the C terminus of retinoblastoma protein [].
The plant-specific protein, TSP9 is phosphorylated and released in response to changing light conditions from the photosynthetic membrane. The protein resembles the characteristics of transcription/translation regulatory factors. The structure of the protein is predicted to consist of a random coil [].
The plant-specific protein, TSP9 is phosphorylated and released in response to changing light conditions from the photosynthetic membrane. The protein resembles the characteristics of transcription/translation regulatory factors. The structure of the protein is predicted to consist of a random coil [].
ATP synthase inhibitor prevents the enzyme from switching to ATP hydrolysis during collapse of the electrochemical gradient, for example during oxygen deprivation []ATP synthase inhibitor forms a one to one complex with the F1 ATPase, possibly by binding at the α-β interface. It is thought to inhibit ATP synthesis by preventing the release of ATP []. The minimum inhibitory region for bovine inhibitor () is from residues 39 to 72 []. The inhibitor has two oligomeric states, dimer (the active state) and tetramer. At low pH , the inhibitor forms a dimer via antiparallel coiled coil interactions between the C-terminal regions of two monomers. At high pH, the inhibitor forms tetramers and higher oligomers by coiled coil interactions involving the N terminus and inhibitory region, thus preventing the inhibitory activity [].
Stathmin [](from the Greek 'stathmos' which means relay), is an ubiquitousintracellular protein, present in a variety of phosphorylated forms and whichis involved in the regulation of the microtubule (MT) filament system bydestabilising microtubules. It prevents assembly and promotes disassembly ofmicrotubules.These proteins possess a stathmin-like domain (SLD) with various N-terminalextensions. SLD is a highly conserved domain of 149 amino acid residues.Structurally, it consists of an N-terminal domain of about 45 residuesfollowed by a 78 residue α-helical domain consisting of a heptad repeatcoiled coil structure and a C-terminal domain of 25 residues[]. The SLD binds two tubulins arranged longitudinally, head-to-tail, in protofilament-like complexes.This entry represents two conserved sites. The first one is a conserved decapeptide which ends with the first three residues of the coiled coil domain. The second conserved site corresponds to part of the central region of the coiled coil.
The MreD (murein formation D) protein is involved in bacterial cell shape determination [, ]. Most rod-shaped bacteria depend on MreB and RodA to achieve either a rod shape or some other non-spherical morphology such as coil or stalk formation. MreD is encoded in an operon with MreB, and often with RodA and PBP-2 as well. It is highly hydrophobic (therefore somewhat low-complexity) and highly divergent, and therefore cannot always be identified on the basis of sequence similarity.
This domain is found at the C terminus of ATP-binding cassette (ABC) transporters such as Uup from Escherichia coli. Uup is a member of the REG subfamily of class II ABC ATPases. It comprises two nucleotide-binding domains (NBD), separated by a 75-residue linker, and a C-terminal domain (CTD). CTD has a coiled coil structure with an atypical 3(10)-helix in the alpha-hairpin region and is involved in DNA binding [].
TRIM10 (also known as HERF1) is a hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells [, ]. TRIM10 belongs to the C-IV 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 B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.
Stomoxyn is an insect antimicrobial peptide localised in the gut epithelium, which functions in killing a range of microorganisms, parasites and some viruses. In water, stomoxyn has a flexible random coil in structure, while in trifluoroethanol it adopts a stable helical structure. Structural similarities to the antimicrobial peptide cecropin A from Hyalophora cecropia suggest that it may function in a similar manner by disrupting the bacterial membrane [].
This entry include a group of Dictyostelium discoideum (Slime mould) proteins, including hssA/B proteins. HssA (also known as NK20) is a high-glycine-serine-rich small protein (8.37kDa), which has strong homology to previously reported cyclic-adenosine-monophosphate-inducible 2C and 7E proteins []. This protein may form extended coil structures []. The serine-rich chaperone protein 1 (hssl63) suppresses aggregation of proteins with long polyglutamine tracts by protoming their degradation by the proteasome [].
This entry represents the N-terminal region of the mammal LETM1-domain-containing protein LETM2, a mitochondrial protein that is expressed preferentially in spermatocytes and spermatozoa during developmental stages from spermatocyte to spermatozoon. LETM2 might contribute to the reorganisation of the inner and cristae membranes during spermatogenesis. Despite its name, it does not contain an EF-hand domain as LETM1, but it contains a putative leucine zipper coiled coil domain [, ].
Oprl is a major outer membrane lipoprotein that contains an alanine-zipper [, ]. Zipper motifs are a seven-repeat motif where the first and fourth positions are occupied by an aliphatic residue, usually a leucine. These residues are positioned on the outside of the coil such as to bind firmly to one or more monomers of the protein to create a triple or five-helical coiled-coil that probably forms a seam in a membrane.
Intermediate filaments (IF) [, ]are proteins which are primordialcomponents of the cytoskeleton and the nuclear envelope. They generally formfilamentous structures 8 to 14 nm wide. IF proteins are members of a verylarge multigene family of proteins which has been subdivided in six types:Type I: Acidic cytokeratins.Type II: Basic cytokeratins.Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP),peripherin, and plasticin.Type IV: Neurofilaments L, H and M, alpha-internexin and nestin.Type V: Nuclear lamins A, B1, B2 and C.Type VI: 'Orphan' IF proteins, which are more distant in terms of theiramino acid sequences.All IF proteins are structurally similar in that they consist of: a centralrod domain comprising some 300 to 350 residues which is arranged in coiled-coiled α-helices, with at least two short characteristic interruptions; aN-terminal non-helical domain (head) of variable length; and a C-terminaldomain (tail) which is also non-helical, and which shows extreme lengthvariation between different IF proteins.While IF proteins are evolutionary and structurally related, they have limitedsequence homologies except in several regions of the rod domain. The IF roddomain is approximately 310 residues long in all cytoplasmic IF proteins andclose to 350 residues in the nuclear ones. The IF rod domain exhibits aninterrupted α-helical conformation and reveals apronouncedseven-residue periodicity in the distribution of apolar residues.The heptad periodicity within the rod domain is interrupted in several places,which generates four consecutive α-helical segments: 1A and 1B, whichtogether form the so-called coil 1, and 2A and 2B, which form coil 2. The fourα-helical segments are interconnected by relatively short, variablelinkers L1, L12 and L2 [, ].IF proteins have a very strong tendency to dimerize via the formation of anα-helical coiled coil (CC) by their rod domains [].
Intermediate filaments (IF) []are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide. IF proteins are members of a very large multigene family of proteins, which has been subdivided in six major subgroups: Type I: Acidic cytokeratins. Type II: Basic cytokeratins. Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin. Type IV: Neurofilaments L, H and M, alpha-internexin and nestin. Type V: Nuclear lamins A, B1, B2 and C. Type VI: 'Orphan' IF proteins, which are more distant in terms of their amino acid sequences. All IF proteins are structurally similar in that they consist of: a centralrod domain comprising some 300 to 350 residues which is arranged in coiled-coiled α-helices, with at least two short characteristic interruptions; aN-terminal non-helical domain (head) of variable length; and a C-terminaldomain (tail) which is also non-helical, and which shows extreme lengthvariation between different IF proteins.While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain. The IF rod domain is approximately 310 residues long in all cytoplasmic IF proteins andclose to 350 residues in the nuclear ones. The IF rod domain exhibits aninterrupted α-helical conformation and reveals apronounced seven-residue periodicity in the distribution of apolar residues.The heptad periodicity within the rod domain is interrupted in several places,which generates four consecutive α-helical segments: 1A and 1B, whichtogether form the so-called coil 1, and 2A and 2B, which form coil 2. The fourα-helical segments are interconnected by relatively short, variablelinkers L1, L12 and L2 [, ].IF proteins have a very strong tendency to dimerize via the formation of anα-helical coiled coil (CC) by their rod domains [].This entry represents a conserved region situated at the very end of the 2B segment, which is critically involved in specific dimer-dimer interactions within the mature filament [].
Tubulin binding cofactor C (TBCC) is a post-chaperonin involved in folding pathways that lead to the final release of alpha beta native heterodimers incorporated in microtubules. TBCC is organised into three different domains: N-terminal, CARP and C-terminal [].This entry represents the N-terminal domain of TBCC. The N-terminal comprises a structured coiled coil and a highly dynamic N-terminal region which concentrates 80% of charged and polar residues and is believed to be important in interaction with tubulin []. Overall, the N-terminal domain of TBCC is responsible for its interaction with components of the centrosome by its N-terminal domain.
The MreD (murein formation D) protein is involved in bacterial cell shape determination [, ]. Most rod-shaped bacteria depend on MreB and RodA to achieve either a rod shape or some other non-spherical morphology such as coil or stalk formation. MreD is encoded in an operon with MreB, and often with RodA and PBP-2 as well. It is highly hydrophobic (therefore somewhat low-complexity) and highly divergent, and therefore cannot always be identified on the basis of sequence similarity.This entry represents the proteobacterial MreD proteins.
The b subunit of the E. coli F-type ATP synthase is present as a dimer and links the peripheral F(1) subunits to the membrane-integral F(0) portion. The dimerisation domain of the b subunit consists of an α-helical coiled-coil structure. In the dimer the two helices form a coiled coil with a right-handed superhelical twist. Analysis of b sequences from other prokaryotes indicates conservation of an undecad repeat in this domain []. This superfamily represents a membrane domain that covers most of the dimerisation domain of the b subunit of the E. coli F-type ATP synthase.
Tubulin binding cofactor C (TBCC) is a post-chaperonin involved in folding pathways that lead to the final release of alpha beta native heterodimers incorporated in microtubules. TBCC is organised into three different domains: N-terminal, CARP and C-terminal [].This entry represents the N-terminal domain of TBCC. The N-terminal comprises a structured coiled coil and a highly dynamic N-terminal region which concentrates 80% of charged and polar residues and is believed to be important in interaction with tubulin []. Overall, the N-terminal domain of TBCC is responsible for its interaction with components of the centrosome by its N-terminal domain.
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 []. This family includes the zeta subunit from the CD3 T-Cell co-receptor.
Apolipoprotein A-II (ApoA-II) is the second major apolipoprotein of high density lipoprotein in human plasma. Mature ApoA-II is present as a dimer of two 77-amino acid chains joined by a disulphide bridge []. ApoA-II regulates many steps in HDL metabolism, and its role in coronary heart disease is unclear []. In bovine serum, the ApoA-II homologue is present in almost free form. Bovine ApoA-II shows antimicrobial activity against Escherichia coli and yeasts in phosphate buffered saline (PBS) [].ApoA-II structure presents a segmented tetrameric parallel coiled coil fold.
ParB is a component of the par system which mediates accurate DNA partition during cell division. It recognises A-box and B-box DNA motifs. ParB forms an asymmetric dimer with 2 extended helix-turn-helix (HTH) motifs that bind to A-boxes. The HTH motifs emanate from a beta sheet coiled coil DNA binding module []. Both DNA binding elements are free to rotate around a flexible linker, this enables them to bind to complex arrays of A- and B-box elements on adjacent DNA arms of the looped partition site [].
Anti-sigma factor A is a transcriptional inhibitor that inhibits sigma 70-directed transcription by weakening its interaction with the core of the host's RNA polymerase. It is an all-helical protein, composed of six helical segments and intervening loops and turns, as well as a helix-turn-helix DNA binding motif, although neither free anti-sigma factor nor anti-sigma factor bound to sigma-70 has been shown to interact directly with DNA. In solution, the protein forms a symmetric dimer of small (10.59kDa) protomers, which are composed of helix and coil regions and are devoid of β-strand/sheet secondary structural elements [].
This is the C-terminal conserved coiled coil region of a family of TATA element modulatory factor 1 proteins conserved in eukaryotes []. The proteins bind to the TATA element of some RNA polymerase II promoters and repress their activity. by competing with the binding of TATA binding protein. TMF1_TATA_bd is the most conserved part of the TMFs []. TMFs are evolutionarily conserved golgins that bind Rab6, a ubiquitous ras-like GTP-binding Golgi protein, and contribute to Golgi organisation in animal []and plant cells. The Rab6-binding domain appears to be the same region as this C-terminal family [].
This is the middle region of a family of TATA element modulatory factor 1 (TMF1) proteins conserved in eukaryotes that contains at its N-terminal section a number of leucine zippers that could potentially form coiled coil structures. The whole proteins bind to the TATA element of some RNA polymerase II promoters and repress their activity by competing with the binding of TATA binding protein. TMFs are evolutionarily conserved golgins that bind Rab6, a ubiquitous ras-like GTP-binding Golgi protein, and contribute to Golgi organisation in animal []and plant []cells.
During the process of Escherichia coli nucleotide excision repair, DNA damagerecognition and processing are achieved by the action of the uvrA, uvrB,and uvrC gene products []. UvrB and UvrC share a common domain of around 35amino acids, the so called UVR domain. This domain in UvrB can interact withthe homologous domain in UvrC throughout a putative coiled coil structure.This interaction is important for the incision of the damaged strand [].A conserved region similar to the UVR domain is also found in the ATP-binding subunit of bacterial and chloroplastic Clp ATPases [], which suggest that the UVR domain is not only involved in the interaction between uvrB and uvrC.
Mitofilin (also known as MICOS complex subunit MIC60) is a component of the MICOS complex which controls mitochondrial cristae morphology, maintenance of junctions, inner membrane architecture, and formation of contact sites to the outer membrane [, ]. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex []. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence (residues 1-43) rich in positive-charged and hydroxylated residues and a membrane anchor domain (residues 47-66). In addition, it has three centrally located coiled coil domains (residues 200-240, 280-310 and 400-420) [].
MukE 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 MreD (murein formation D) protein is involved in bacterial cell shape determination. Most rod-shaped bacteria depend on MreB and RodA to achieve either a rod shape or some other non-spherical morphology such as coil or stalk formation. MreD is encoded in an operon with MreB, and often with RodA and PBP-2 as well. It is highly hydrophobic (therefore somewhat low-complexity) and highly divergent, and therefore cannot always be identified on the basis of sequence similarity.This group represents predicted MreD proteins found primarily in Clostridium and Treponema species.
MukE 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 besimilar 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. This superfamily represents the MukE C-terminal domain. Structurally, it consists of 4 helices and 3 small beta strands.
MukE 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. This superfamily represents the MukE N-terminal domain. Structurally, it consists of 3 helices and 2 small beta strands.
This family contains proteins of up to five transmembranes helices found in bacterial species, some of which carry a nested PepSY domain. Coil residues are significantly more conserved than other residues and are frequently found within channels and transporters, where they introduce the flexibility and polarity required for transport across the membrane [].PepSY (peptidase (M4) and YpeB of subtilis) is a repeated region first identified in Thermoanaerobacter tengcongensis. The PepSY domain functions in the control of M4 peptidases through their propeptide and in the germination of spores. It may also play a part in regulating protease activity [].
This family contains MukF, which are proteins involved in chromosome condensation, segregation and cell cycle progression. 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 MuKF has been revealed [].
Proteins in this family adopt a coiled coil structure, with two antiparallel α-helices that are tightly strapped together by two disulfide bridges at each end. The protein sequence shows a cysteine motif, required for the stabilisation of the coiled-coil-like structure. Additional inter-helix hydrophobic contacts impart stability to this scaffold [].The precise function of this family is, as yet, unknown []. MTCP1 is found in mitochondria. Mature-T-Cell Proliferation is the first gene unequivocally identified in the group of uncommon leukemias with a mature phenotype [].
TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization. TRIM58 belongs to the C-IV 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 B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain [].
Anti-sigma factor A is a transcriptional inhibitor that inhibits sigma 70-directed transcription by weakening its interaction with the core of the host's RNA polymerase. It is an all-helical protein, composed of six helical segments and intervening loops and turns, as well as a helix-turn-helix DNA binding motif, although neither free anti-sigma factor nor anti-sigma factor bound to sigma-70 has been shown to interact directly with DNA. In solution, the protein forms a symmetric dimer of small (10.59kDa) protomers, which are composed of helix and coil regions and are devoid of β-strand/sheet secondary structural elements [].
Tripartite motif-containing protein 42 (TRIM42) belongs to the C-III 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 domain. It also has a novel cysteine-rich motif N-terminal to the RBCC domain, as well as a COS (carboxyl-terminal subgroup one signature) box and a fibronectin type-III (FN3) domain positioned C-terminal to the RBCC domain. TRIM42 can interact with TRIM27, a known cancer-associated protein. Its precise biological function remains unclear [, ].
Tiam1 is a guanine exchange factor (GEF) for CDC42 and the Rho-family GTPase Rac1, which plays an important role in cell-matrix adhesion and in cell migration [, ]. Tiam1 is involved in multiple steps of tumorigenesis [].This entry represents the CC and Ex subdomain found in the PH-CC-Ex globular domain of the Tiam1 and Tiam2 proteins (T-lymphoma invasion and metastasis). The CC subdomain forms an antiparallel coiled coil with two long α-helices, together with the C-terminal Ex subdomain they form a small globular domain comprising three α-helices. The CC subdomain of the Tiam2 PHCCEx domain follows the C-terminal alpha1 helix of the PH subdomain through a four-residue linker [].
This is the C-terminal domain of BRCC36, a Zn2+ dependent deubiquitinating enzyme, present in Camponotus floridanus. BRCC36 hydrolyzes lysine linked ubiquitin chains as part of macromolecular complexes that participate in either interferon signalling or DNA-damage recognition. The domain consists of 2 non canonical helices. The domain interacts hydrophobically with helices alpha 4 and alpha 5 of KIAA0157 in the form of a coiled coil helical bundle. This interaction helps establish the association of BRCC36 with KIAA0157, a pseudo-DUB MPN- protein that is essential for theactivity of BRCC36 [].
During the process of Escherichia coli nucleotide excision repair, DNA damagerecognition and processing are achieved by the action of the uvrA, uvrB,and uvrC gene products []. UvrB and UvrC share a common domain of around 35amino acids, the so called UVR domain. This domain in UvrB can interact withthe homologous domain in UvrC throughout a putative coiled coil structure.This interaction is important for the incision of the damaged strand [].A conserved region similar to the UVR domain is also found in the ATP-binding subunit of bacterial and chloroplastic Clp ATPases [], which suggest that the UVR domain is not only involved in the interaction between uvrB and uvrC.
R-bodies are highly insoluble protein ribbons which coil into cylindrical structures in the cell and the genes for their synthesis and assembly are encoded on a plasmid. One of these three proteins is RebB, which this entry represents.RebB is one of three proteins necessary for the production of R- bodies, refractile inclusion bodies produced by a small number of bacterial species, essential for the expression of the killing trait of the endosymbiont bacteria that produce them for attack upon the host Paramecium. Note that many members are uncharacterised proteins [, ].
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 ().
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 ().
A conserved motif was identified in the LOC118487 protein was called the CHCH motif. Alignment of this protein with related members showed the presence of three subgroups of proteins, which are called the S (Small), N (N-terminal extended) and C (C-terminal extended) subgroups. All three sub-groups of proteins have in common that they contain a predicted conserved [coiled coil 1]-[helix 1]-[coiled coil 2]-[helix 2]domain (CHCH domain). Within each helix of the CHCH domain, there are two cysteines present in a C-X9-C motif. The N-group contains an additional double helix domain, and each helix contains the C-X9-C motif. This family contains a number of characterised proteins: Cox19 protein - a nuclear gene of Saccharomyces cerevisiae, codes for an 11kDa protein (Cox19p) required for expression of cytochrome oxidase. Because cox19 mutants are able to synthesise the mitochondrial and nuclear gene products of cytochrome oxidase, Cox19p probably functions post-translationally during assembly of the enzyme. Cox19p is present in the cytoplasm and mitochondria, where it exists as a soluble intermembrane protein. This dual location is similar to what was previously reported for Cox17p, a low molecular weight copper protein thought to be required for maturation of the CuA centre of subunit 2 of cytochrome oxidase. Cox19p have four conserved potential metal ligands, these are three cysteines and one histidine. Mrp10 - belongs to the class of yeast mitochondrial ribosomal proteins that are essential for translation []. Eukaryotic NADH-ubiquinone oxidoreductase 19kDa (NDUFA8) subunit []. The CHCH domain was previously called DUF657 [].
This family includes WD repeat and coiled-coil-containing protein (WDCP, previously known as C2orf44), which is found in eukaryotes and consists of around 721 amino acids. The N-terminal contains two WD (tryptophan-aspartic acid) repeats (WD1 and WD2). WD repeats may be involved in a range of biological functions including apoptosis, transcriptional regulation and signal transduction. The C-terminal contains a proline-rich sequence (PPRLPQR), and is predicted to have leucine-rich coiled coil region (CC) [].WDCP was identified in a proteomic screen to find signalling components that interact with Hck (hematopoietic cell kinase), a non-receptor tyrosine kinase. WDCP was shown to bind tightly and specifically to the SH3 domain of Hck in U937 human monocytic cells. WDCP was also shown to exist as an oligomer when expressed in mammalian cells. While the function of WDCP is unknown, it has been identified in a gene fusion event with anaplastic lymphoma kinase (ALK) in colorectal cancer patients [].
This domain identifies a group of proteins, which are described as: General vesicular transport factor, Transcytosis associate protein (TAP) and Vesicle docking protein. This myosin-shaped molecule consists of an N-terminal globular head region, a coiled-coil tail which mediates dimerisation, and a short C-terminal acidic region []. p115 tethers COP1 vesicles to the Golgi by binding the coiled coil proteins giantin (on the vesicles) and GM130 (on the Golgi), via its C-terminal acidic region. It is required for intercisternal transport in the Golgi stack. This domain is found in the acidic C-terminal region, which binds to the golgins giantin and GM130. p115 is thought to juxtapose two membranes by binding giantin with one acidic region, and GM130 with another [].
This domain identifies a group of proteins, which are described as: General vesicular transport factor, Transcytosis associated protein (TAP) or Vesicle docking protein, this myosin-shaped molecule consists of an N-terminal globular head region, a coiled-coil tail which mediates dimerisation, and a short C-terminal acidic region []. p115 tethers COP1 vesicles to the Golgi by binding the coiled coil proteins giantin (on the vesicles) and GM130 (on the Golgi), via its C-terminal acidic region. It is required for intercisternal transport in the Golgi stack. This domain is found in the head region. The head region is highly conserved, but its function is unknown. It does not seem to be essential for vesicle tethering []. The N-terminal part of the head region contains context-detected Armadillo/beta-catenin-like repeats.
This is the C-terminal MrfA (Mitomycin repair factor A, also known as YprA in Bacillus subtilis) Zn+2-binding domain (MZB, also referred to as DUF1998) which contains a conserved four-cysteine signature motif. These four Cys reside in a short coil between two α-helices and form a metal ion-binding site []. This domain is frequently found at the C-terminal of ndNTPases, however, it is also found encoded in a standalone gene, downstream of putative helicase domain-encoding genes associated with bacterial anti-phage defense system DISARM. MrfA is a DNA helicase that supports repair of mitomycin C-induced DNA damage. MrfA homologues are widely distributed in bacteria and are also present in archaea, fungi and plants. The MrfA-homologue in yeast, Hrq1, also reduces mitomycin C sensitivity. Hrq1 has high similarity to human RecQ4 and was therefore assigned to the RecQ-like helicase family []. MrfA homologues appear to be missing in Enterobacteria, however, certain pathogenic Escherichia coli and Salmonella strains harbour Z5898-like helicases with this domain [].
Non-structural protein NSP7 has been implicated in viral RNA replication and is predominantly α-helical in structure. Its central core is an N-terminal helical bundle (HB), with helices HB1, HB2 and HB3, forming a triple-stranded antiparallel coiled coil with a right-handed superhelical pitch. It is part of the RNA-dependent RNA polymerase (RdRp) heterotetramer which consists of one NSP7, two NSP8 molecules and the catalytic NSP12, defined as the minimal core component for mediating coronavirus RNA synthesis [, , , , , ]. NSP7 and NSP8 forms a complex that adopts a hollow cylinder-like structure []. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase []. NSP7 and NSP8 play a role in the stabilisation of NSP12 regions involved in RNA binding, and are essential for a highly active NSP12 polymerase complex [, , , ].
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 shown to 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 [, , ].
In prokaryotes, the nucleotideexchange 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. The head domain is comprised of six short beta strands with a limited hydrophobic core.
The RH1 (RILP homology 1) protein-protein interaction domain is found in thefollowing animal Rab36-binding proteins:Rab interacting lysosomal proteins (RILP),RILP-like 1 (RILP-L1),RILP-like 2 (RILP-L2),JNK-interacting protein 3 (JIP3),JNK-interacting protein 4 (JIP4).It binds to the myosin Va globular tail domain (MyoVa-GTD) in mainlyhydrophobic interactions.The RH1 domain adopts an all-helical structure and forms ahomodimer with a four-helix bundle conformation to interact with MyoVa-GTD.The RH1 homodimer is structurally separated into two parts, the N-terminalfour-helix bundle formed by alpha2 and alpha3N and the C-terminal coiled-coilformed by alpha3C. The four-helix bundle in the RH1 dimer is mainly stabilizedby forming a hydrophobic core. The N-terminal small helix (alpha1) and itsfollowing loop pack on alpha2 from the same molecule and alpha3 from theneighbouring molecule and thus contribute to the bundle stability. The RH1homodimer is further strengthened by a coiled coil formed by the C-terminalhalf of the alpha3-helix [].This entry represents the entire RH1 domain.
TRIM68 is an E3 ubiquitin-protein ligase that negatively regulates Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I interferon production by degrading TRK fused gene (TFG), a novel driver of IFN-beta downstream of anti-viral detection systems []. It also functions as a cofactor for androgen receptor-mediated transcription through regulating ligand-dependent transcription of androgen receptor in prostate cancer cells []. Moreover, TRIM68 is a cellular target of autoantibody responses in Sjogren"s syndrome (SS), as well as systemic lupus erythematosus (SLE). It is also an auto-antigen for T cells in SS and SLE [, ]. TRIM68 belongs the C-IV 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, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. This entry represents the C3HC4-type RING-HC finger found in TRIM68.
Microtubule-associated protein RP/EB family member 1 (EB1) belongs to the RP/EB family, which consists of MAPRE1 (EB1), MAPRE2 (RP1, also known as EB2) and MAPRE3 (EBF3, also known as EB3). EB1 binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. 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 [].
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 [, , , , , , , ].Some proteins known to contain a NPH3 domain include:Arabidopsis non-phototropic hypocotyl 3 (NPH3), may function as an adapteror scaffold protein in plants.Arabidopsis root-phototropisme 2 (RPT2), a signal transducer involved inphototropic response and stomatal opening in association with phototropin 1(phot1).Oriza coleoptile phototropism 1 (CPT1), the rice ortholog of NPH3. It isrequired for phototropism of coleoptiles and lateral translocation ofauxin.This entry represents the NPH3 domain.
This domain is found at the C-terminal region of Hop2 and Mnd1 proteins. In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex. Hop2 (for homologous pairing; also known as TBPIP) is expressed specifically during meiosis, same as Mnd1 (for meiotic nuclear divisions 1). The C-terminal region of both Hop2 and Mnd1, folds into three α-helices that are interrupted by two short non-helical regions. These α-helices of the two proteins together form a parallel coiled coil that provides the major interface for heterodimer formation. The non-helical regions form substantially kinked junctions between adjacent leucine zippers: the LZ1-LZ2 and LZ2-LZ3 junctions.This domain is the C-terminal segment of Hop2 and Mnd1 which folds back onto the C-terminal leucine zipper (LZ3) to form a helical bundle-like structure, hence designated LZ3wCH (for LZ3 with capping helices). The LZ3wCH region plays a role in interacting with the Dmc1 nucleofilament [].
Non-structural protein NSP7 has been implicated in viral RNA replication and is predominantly α-helical in structure. Its central core is an N-terminal helical bundle (HB), with helices HB1, HB2 and HB3, forming a triple-stranded antiparallel coiled coil with a right-handed superhelical pitch. It is part of the RNA-dependent RNA polymerase (RdRp) heterotetramer which consists of one NSP7, two NSP8 molecules and the catalytic NSP12, defined as the minimal core component for mediating coronavirus RNA synthesis [, , , , , ]. NSP7 and NSP8 forms a complex that adopts a hollow cylinder-like structure []. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase []. NSP7 and NSP8 play a role in the stabilisation of NSP12 regions involved in RNA binding, and are essential for a highly active NSP12 polymerase complex [, , , ].
The MRN complex (Mre11-Rad50-Nbs1) plays an important role in many DNA metabolic events that involve DNA double-stranded breaks. MRN is one of the first factors to be localised to DNA lesions where it might have a structural role by tethering and stabilising broken chromosomes [, ]. Rad50 is a split ABC-type ATPase; its centre contains a long heptad repeat that folds into an antiparallel coiled coil, bringing the N-terminal (Walker A) and the C-terminal (Walker B) domains in close proximity []. The apex of the coiled coil contains a dimerization interface, a conserved Cys-X-X-Cys motif in a hook-shaped domain that dimerizes with a second hook domain via cysteine-mediated zinc ion coordination. This zinc dependent dimerization event allows the formation of a complex that has appropriate lengths and conformational proporties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining.
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 [].
Microbial pectin and pectate lyases are virulence factors that degrade the pectic components of the plant cell wall []. When the backbone of pectin is methylated it is known as pectin and is cleaved by pectin lyase, and when it is demethylated it is known as pectate and is cleaved by pectate lyase. Pectin lyase from Aspergillus niger displays a single-stranded, right-handed parallel β-helix topology (), where each coil contains three β-strands and three turn regions. Several other virulence factors share this β-helix topology, although they vary in the number of coils, including bacterial pectate lyases, fungal and bacterial galacturonases (such as rhamnogalacturonase and polygalacturonase), chrondroitinase B from Flavobacterium sp., iota-carrageenase from Alteromonas sp., pectin methylesterase (PemA), P22 tailspike protein from Enterobacteria phage P22, and the virulence factor P.69 pertactin from Bordetella pertussis that mediates adhesion to target mammalian cells [].
TRIM72, also known as MG53, is a cardiac and skeletal muscle-specific TRIM protein. It is involved in cardiac and skeletal muscle membrane repair []. TRIM72 initiates the assembly of cell membrane repair machinery at sarcolemmal membrane injury sites in response to entry of the extracellular oxidative environment []. As an E3 ligase, it negatively regulates skeletal myogenesis and insulin signalling by targeting insulin receptor substrate 1 (IRS-1) [].Tripartite Motif (TRIM) family members share a common domain architecture characterised by the presence of a modular N-terminal RBCC motif, also called the TRIM, which consists of a RING domain, followed by one or two B-box domains and a long coiled coil (CC) region. The RBCC motif is followed by C-terminal functional domains that are often used to categorise family members into subgroups [].TRIM72 C terminus consists of the distinct N-terminal PRY subdomain followed by the SPRY subdomain.
