This entry represents the Cys/His rich zinc-binding domain (ZBD) of SF1 helicase from tornidovirus which includes White bream virus (WBV). This domain has 3 zinc-finger motifs []. This group of viruses belong to Nidovirales order and it shares the same genome organisation. It encodes the large polyprotein pp1a which is then proteolytically processed to produce the enzymes required for the replicative machinery. This is a novel cluster of nidoviruses that significantly diverged from toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses [].
This entry represents an uncharacterised domain located between the Cys/His zinc-binding domain (ZBD) and the first helicase domain found in helicases from Gill-associated virus (GAV) and related viruses from ronidovirus family. It is thought to be a linker domain. They are related to the SF1 family of nidoviral replication helicases, similar to the Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-NSP13) helicase (not included in this entry), which share a similar domain organisation. The location and orientation of this uncharacterized domain represented in this ronidovirus group resembles that of the 1B domain in SARS-NSP13 helicase [, ].
This entry represents the Cys/His rich zinc-binding domain (ZBD) of the helicase encoded on ORF1a and belongs to helicase superfamily 1 (SF1) from ronidovirus family including Gill-associated virus (GAV) []. The ZBD has 3 zinc-finger (ZnF1-3) motifs. Proteins containing this domain belong to a family of nindoviral replication helicases similar to SARS-NSP13 helicase, not included in this entry. The SARS-NSP13 ZBD is indispensable for helicase activity and interacts with SARS-Nsp12. SARS-Nsp12 can enhance the helicase activity of SARS-Nsp13 and can interact with SARS-Nsp13 on the third zinc finger motif of the ZBD [].
This entry represents an uncharacterised domain found in SF1 helicases from tornidovirus, including Breda virus serotype 1. This group of viruses belong to Nidovirales order and it shares the same genome organisation. It encodes the large polyprotein pp1a which is then proteolytically processed to produce the enzymes required for the replicative machinery. This is a novel cluster of nidoviruses that significantly diverged from toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses []. This domain connects the zinc-binding domain (ZBD) with the first helicase domain, resembling that of the 1B domain in SARS-Nsp13 helicase [, ].
This domain contains a P-loop (Walker A) motif, suggesting that it has ATPase activity, and a Walker B motif. In tRNA(Met) cytidine acetyltransferase (TmcA) it may function as an RNA helicase motor (driven by ATP hydrolysis) which delivers the wobble base to the active centre of the GCN5-related N-acetyltransferase (GNAT) domain []. It is found in the bacterial exodeoxyribonuclease V alpha chain (RecD), which has 5'-3' helicase activity. It is structurally similar to the motor domain 1A in other SF1 helicases [].
RNA helicases from the DEAD-box family are found in almost all organisms andhave important roles in RNA metabolism, such as splicing, RNA transport,ribosome biogenesis, translation and RNA decay. They are enzymes that unwinddouble-stranded RNA molecules in an energy dependent fashion through thehydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) ofhelicases. As other SF1 and SF2 members they contain seven conserved motifswhich are characteristic of these two superfamilies [].DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-bindingaspartic acid). The RNA helicase DbpA has an RNA-dependent ATPase activity, which is specific for 23S rRNA [, ]. It is involved in assembly of the 50S ribosomal subunit [].
RNA helicases from the DEAD-box family are found in almost all organisms andhave important roles in RNA metabolism, such as splicing, RNA transport,ribosome biogenesis, translation and RNA decay. They are enzymes that unwinddouble-stranded RNA molecules in an energy dependent fashion through thehydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) ofhelicases. As other SF1 and SF2 members they contain seven conserved motifswhich are characteristic of these two superfamilies [].DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-bindingaspartic acid). SrmB is a DEAD-box RNA helicase that is involved in ribosome assembly. Deletion of the srmB gene in Escherichia coli causes a slow-growth phenotype at low temperature [].
RecBCD is a multi-functional enzyme complex that processes DNA ends resulting from a double-strand break. RecBCD is a bipolar helicase that splits the duplex into its component strands and digests them until encountering a recombinational hotspot (Chi site) []. The RecD subunit accounts for the 5'-3' helicase activity of RecBCD. The structure of the RecD subunit resembles SF1 helicase. RecD comprises several domains - N-terminal domain, domains 1A, 1B, 2A (or 3) and 2B (in D. radiodurans RecD2) []. This superfamily entry represents the N-terminal domain of RecD subunit.
This entry includes TCRG1/TCRGL from human and related proteins from animals, fungi and plants. TCRG1 (also known as CA150) contains three N-terminal WW domains and six consecutive FF domains. WW and FF domains are versatile modules that mediate protein-protein interactions []. TCRG1 is a transcription elongation factor that interacts with the splicing factor SF1 and with the phosphorylated C-terminal repeat domain (CTD) of RNA polymerase II (RNAPII) through its WW and FF domains, respectively [].This entry also includes Urn1 from budding yeasts and PRP40C from Arabidopsis. They are predicted to be involved in pre-mRNA splicing [].
Helicases have been classified in 6 superfamilies (SF1-SF6) []. All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) and Walker B (Mg2+-binding aspartic acid) motifs. The two largest superfamilies,commonly referred to as SF1 and SF2, share similar patterns of seven conserved sequence motifs, some of which are separated by long poorly conserved spacers. Helicase motifs appear to be organised in a core domain which provides the catalytic function, whereas optional inserts and amino- and carboxy-terminal sequences may comprise distinct domains with diverse accessory roles. The helicase core contains two structural domains, an N-terminal ATP-binding domain and a C-terminal domain. Putative SF1 helicases are extremely widespread among positive-stranded (+)RNA viruses. They have been identified in a variety of plant virus families, as well as alpha- rubi-, arteri-, hepatitis E, and coronaviruses. A number of these viral enzymes have been implicated in diverse aspects of transcription and replication but also in RNA stability and cell-to-cell movement [].The (+) RNA virus helicase core contains two RecA-like α/β domains. The N-terminal ATP-binding domain contains a parallel six-stranded β-sheet surrounded by four helices on one side and two helices on the other. The C-terminal domain contains a parallel four-stranded β-sheetsandwiched between two helices on each of its sides. The (+)RNA virus helicase core is likely to bind NTP in cleft between the N terminus of the ATP-binding domain and the beginning of the C-terminal domain [].This entry represents the (+)RNA virus helicase core domain.
This entry represents a group of helicases, including DNA2 and Nam7. Proteins in this family contain a conserved domain with s a P-loop motif that is characteristic of the AAA superfamily. They are DEAD-like helicases belonging to superfamily (SF)1, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF2 helicases, SF1 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA [, , ].Dna2 is a DNA replication factor with single-stranded DNA-dependent ATPase, ATP-dependent nuclease, (5'-flap endonuclease) and helicase activities [, ]. Nam7 (also known as Upf1) is an ATP-dependent RNA helicase involved in the nonsense-mediated mRNA decay (NMD) pathway [].
RNA helicases from the DEAD-box family are found in almost all organisms andhave important roles in RNA metabolism, such as splicing, RNA transport,ribosome biogenesis, translation and RNA decay. They are enzymes that unwinddouble-stranded RNA molecules in an energy dependent fashion through thehydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) ofhelicases. As other SF1 and SF2 members they contain seven conserved motifswhich are characteristic of these two superfamilies [].DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-bindingaspartic acid). The RNA helicase DeaD is ATP-dependent []and is induced by low temperatures []. In addition to its role in unwinding double stranded RNA, it is involved in ribosomal subunit biogenesis [].
RNA helicases from the DEAD-box family are found in almost all organisms andhave important roles in RNA metabolism, such as splicing, RNA transport,ribosome biogenesis, translation and RNA decay. They are enzymes that unwinddouble-stranded RNA molecules in an energy dependent fashion through thehydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) ofhelicases. As other SF1 and SF2 members they contain seven conserved motifswhich are characteristic of these two superfamilies [].DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-bindingaspartic acid). RhlE is a DEAD-box RNA helicase that is involved in ribosome assembly. It may play a role in the interconversion of ribosomal RNA-folding intermediates that are further processed by DeaD or SrmB during ribosome maturation [].
This domain contains a P-loop motif that is characteristic of the AAA superfamily. Proteins containing this domain are DEAD-like helicases belonging to superfamily (SF)1, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF2 helicases, SF1 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA [, , ].Proteins containing this domain include helicases, such as Dna2 an Nam7. Dna2 is a DNA replication factor with single-stranded DNA-dependent ATPase, ATP-dependent nuclease, (5'-flap endonuclease) and helicase activities [, ]. Nam7 (also known as Upf1) is an ATP-dependent RNA helicase involved in the nonsense-mediated mRNA decay (NMD) pathway []. This domain can also be found in some virus polyproteins. This domain is also known as HelicC.
This entry represents the RNA recognition motif (RRM) of SPF45. SPF45, also termed RNA-binding motif protein 17 (RBM17), is an RNA-binding protein consisting of an unstructured N-terminal region, followed by a G-patch motif and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbours a RNA recognition motif (RRM) and an Arg-Xaa-Phe sequence motif. SPF45 is a bifunctional protein that functions in splicing and DNA repair. It is involved in regulating alternative splicing of the apoptosis regulatory gene FAS (also called CD95). Its UHM binds UHM-ligand motifs (ULMs) present in the 3' splice site-recognizing factors U2AF65, SF1 and SF3b155 []. It binds to the Holliday junction, which is a key DNA intermediate in the homologous-recombination pathway [, ].
Nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) feature the most complex genetic organization among plus-strand RNA viruses. Their replicase genes encode an exceptionally large replicase polyprotein 1a/ab which is then proteolytically processed to release different nonstructural proteins (NSPs) that mediate the key functions required for replication and transcription. One of these NSPs, called NSP10 in arteriviruses (Av) and NSP13 in coronaviruses (CoV) functions as a helicase [, ]. It is a multidomain protein consisting of a N-terminal Cys/His rich zinc-binding domain (ZBD) and a helicase core that belongs to the superfamily SF1 of helicases. The helicase core contains two RecA1 and RecA2 domains and a 1B domain [].This entry represents the 1B domain, which has a regulatory role modulating the nucleic acid substrate binding. Based on the structures from the Equine arteritis virus (EAV) NSP10, 1B domain undergoes large conformational change upon substrate binding, and forms a channel together with 1A and 2A domains that accommodates the single stranded nucleic acids [, ].
This helix-hairpin domain can be found in N-terminal region of mammalian splicing factor 1 (SF1) and fungal branchpoint binding proteins (BBP) []. These proteins are required for pre-spliceosome formation, which is the first step of pre-mRNA splicing [, ]. SF1 forms a complex with U2AF65 through the interaction between this domain and the C-terminal U2AF homology motif domain (UHM) of U2AF65. This domain forms a secondary, hydrophobic interface with U2AF65(UHM) to lock the orientation of the two subunits, which is essential for cooperative formation of the ternary SF1-U2AF65-RNA complex []. This domain contains a highly conserved SPSP motif at its C terminus; the phophorylation of the SPSP motif induces a disorder-to-order transition within a novel SF1/U2AF65 interface [].
Helicases have been classified in 5 superfamilies (SF1-SF5). For the two largest groups, commonly referred to as SF1 and SF2, a total of seven characteristic motifs has been identified []. These two superfamilies encompass a large number of DNA and RNA helicases from archaea, eubacteria, eukaryotes and viruses.This entry represents the C-terminal domain found in proteins belonging to the helicase superfamilies 1 and 2. Included in this group is the eukaryotic translation initiation factor 4A (eIF4A), a member of the DEA(D/H)-box RNA helicase family. The structure of the carboxyl-terminal domain of eIF4A has been determined; it has a parallel α-β topology that superimposes, with minor variations, on the structures and conserved motifs of the equivalent domain in other, distantly related helicases [].
Helicases have been classified in 5 superfamilies (SF1-SF5). All of the proteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. For the two largest groups, commonlyreferred to as SF1 and SF2, a total of seven characteristic motifs has beenidentified []. These two superfamilies encompass a large number of DNA andRNA helicases from archaea, eubacteria, eukaryotes and viruses that seem to beactive as monomers or dimers. RNA and DNA helicases are considered to beenzymes that catalyze the separation of double-stranded nucleic acids in anenergy-dependent manner [].The various structures of SF1 and SF2 helicases present a common core with twoα-β RecA-like domains [, ]. Thestructural homology with the RecA recombination protein covers the fivecontiguous parallel beta strands and the tandem alpha helices. ATP binds tothe amino proximal α-β domain, where the Walker A (motif I) and WalkerB (motif II) are found. The N-terminal domain also contains motif III (S-A-T)which was proposed to participate in linking ATPase and helicase activities.The carboxy-terminal α-β domain is structurally very similar to theproximal one even though it is bereft of an ATP-binding site, suggesting thatit may have originally arisen through gene duplication of the first one.Some members of helicase superfamilies 1 and 2 are listed below:DEAD-box RNA helicases. The prototype of DEAD-boxproteins is the translation initiation factor eIF4A. The eIF4A protein isan RNA-dependent ATPase which functions together with eIF4B as an RNAhelicase [].DEAH-box RNA helicases. Mainly pre-mRNA-splicing factorATP-dependent RNA helicases [].Eukaryotic DNA repair helicase RAD3/ERCC-2, an ATP-dependent 5'-3' DNAhelicase involved in nucleotide excision repair of UV-damaged DNA.Eukaryotic TFIIH basal transcription factor complex helicase XPB subunit.An ATP-dependent 3'-5' DNA helicase which is a component of the core-TFIIHbasal transcription factor, involved in nucleotide excision repair (NER) ofDNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.It acts by opening DNA either around the RNA transcription start site orthe DNA.Eukaryotic ATP-dependent DNA helicase Q. A DNA helicase that may play arole in the repair of DNA that is damaged by ultraviolet light or othermutagens.Bacterial and eukaryotic antiviral SKI2-like helicase. SKI2 has a role inthe 3'-mRNA degradation pathway, repressing dsRNA virus propagation byspecifically blocking translation of viral mRNAs, perhaps recognizing theabsence of CAP or poly(A).Bacterial DNA-damage-inducible protein G (DinG). A probable helicaseinvolved in DNA repair and perhaps also replication [].Bacterial primosomal protein N' (PriA). PriA protein is one of sevenproteins that make up the restart primosome, an apparatus that promotesassembly of replisomes at recombination intermediates and stalledreplication forks.Bacterial ATP-dependent DNA helicase recG. It has a critical role inrecombination and DNA repair, helping process Holliday junctionintermediates to mature products by catalyzing branch migration. It has aDNA unwinding activity characteristic of helicases with a 3' to 5'polarity.A variety of DNA and RNA virus helicases and transcription factorsThis entry represents the DNA-binding domain of classical SF1 and SF2 helicases. It does not recognize bacterial DinG and eukaryotic Rad3 which differ from other SF1-SF2 helicases by the presence of a large insert after the Walker A (see ).
Helicases have been classified in 5 superfamilies (SF1-SF5). All of the proteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. For the two largest groups, commonlyreferred to as SF1 and SF2, a total of seven characteristic motifs has beenidentified []. These two superfamilies encompass a large number of DNA andRNA helicases from archaea, eubacteria, eukaryotes and viruses that seem to beactive as monomers or dimers. RNA and DNA helicases are considered to beenzymes that catalyze the separation of double-stranded nucleic acids in anenergy-dependent manner [].The various structures of SF1 and SF2 helicases present a common core with twoα-β RecA-like domains [, ]. Thestructural homology with the RecA recombination protein covers the fivecontiguous parallel beta strands and the tandem alpha helices. ATP binds tothe amino proximal α-β domain, where the Walker A (motif I) and WalkerB (motif II) are found. The N-terminal domain also contains motif III (S-A-T)which was proposed to participate in linking ATPase and helicase activities.The carboxy-terminal α-β domain is structurally very similar to theproximal one even though it is bereft of an ATP-binding site, suggesting thatit may have originally arisen through gene duplication of the first one.Some members of helicase superfamilies 1 and 2 are listed below:DEAD-box RNA helicases. The prototype ofDEAD-boxproteins is the translation initiation factor eIF4A. The eIF4A protein isan RNA-dependent ATPase which functions together with eIF4B as an RNAhelicase [].DEAH-box RNA helicases. Mainly pre-mRNA-splicing factorATP-dependent RNA helicases [].Eukaryotic DNA repair helicase RAD3/ERCC-2, an ATP-dependent 5'-3' DNAhelicase involved in nucleotide excision repair of UV-damaged DNA.Eukaryotic TFIIH basal transcription factor complex helicase XPB subunit.An ATP-dependent 3'-5' DNA helicase which is a component of the core-TFIIHbasal transcription factor, involved in nucleotide excision repair (NER) ofDNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.It acts by opening DNA either around the RNA transcription start site orthe DNA.Eukaryotic ATP-dependent DNA helicase Q. A DNA helicase that may play arole in the repair of DNA that is damaged by ultraviolet light or othermutagens.Bacterial and eukaryotic antiviral SKI2-like helicase. SKI2 has a role inthe 3'-mRNA degradation pathway, repressing dsRNA virus propagation byspecifically blocking translation of viral mRNAs, perhaps recognizing theabsence of CAP or poly(A).Bacterial DNA-damage-inducible protein G (DinG). A probable helicaseinvolved in DNA repair and perhaps also replication [].Bacterial primosomal protein N' (PriA). PriA protein is one of sevenproteins that make up the restart primosome, an apparatus that promotesassembly of replisomes at recombination intermediates and stalledreplication forks.Bacterial ATP-dependent DNA helicase recG. It has a critical role inrecombination and DNA repair, helping process Holliday junctionintermediates to mature products by catalyzing branch migration. It has aDNA unwinding activity characteristic of helicases with a 3' to 5'polarity.A variety of DNA and RNA virus helicases and transcription factorsThis entry represents the ATP-binding domain found within bacterial DinG and eukaryotic Rad3 proteins, differing from other SF1 and SF2 helicases by the presence of a large insert after the Walker A motif [].
Helicases have been classified in 5 superfamilies (SF1-SF5). All of the proteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. For the two largest groups, commonlyreferred to as SF1 and SF2, a total of seven characteristic motifs has beenidentified []. These two superfamilies encompass a large number of DNA andRNA helicases from archaea, eubacteria, eukaryotes and viruses that seem to beactive as monomers or dimers. RNA and DNA helicases are considered to beenzymes that catalyze the separation of double-stranded nucleic acids in anenergy-dependent manner [].The various structures of SF1 and SF2 helicases present a common core with twoα-β RecA-like domains [, ]. Thestructural homology with the RecA recombination protein covers the fivecontiguous parallel beta strands and the tandem alpha helices. ATP binds tothe amino proximal α-β domain, where the Walker A (motif I) and WalkerB (motif II) are found. The N-terminal domain also contains motif III (S-A-T)which was proposed to participate in linking ATPase and helicase activities.The carboxy-terminal α-β domain is structurally very similar to theproximal one even though it is bereft of an ATP-binding site, suggesting thatit may have originally arisen through gene duplication of the first one.Some members of helicase superfamilies 1 and 2 are listed below:DEAD-box RNA helicases. The prototype of DEAD-boxproteins is the translation initiation factor eIF4A. The eIF4A protein isan RNA-dependent ATPase which functions together with eIF4B as an RNAhelicase [].DEAH-box RNA helicases. Mainly pre-mRNA-splicing factorATP-dependent RNA helicases [].Eukaryotic DNA repair helicase RAD3/ERCC-2, an ATP-dependent 5'-3' DNAhelicase involved in nucleotide excision repair of UV-damaged DNA.Eukaryotic TFIIH basal transcription factor complex helicase XPB subunit.An ATP-dependent 3'-5' DNA helicase which is a component of the core-TFIIHbasal transcription factor, involved in nucleotide excision repair (NER) ofDNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.It acts by opening DNA either around the RNA transcription start site orthe DNA.Eukaryotic ATP-dependent DNA helicase Q. A DNA helicase that may play arole in the repair of DNA that is damaged by ultraviolet light or othermutagens.Bacterial and eukaryotic antiviral SKI2-like helicase. SKI2 has a role inthe 3'-mRNA degradation pathway, repressing dsRNA virus propagation byspecifically blocking translation of viral mRNAs, perhaps recognizing theabsence of CAP or poly(A).Bacterial DNA-damage-inducible protein G (DinG). A probable helicaseinvolved in DNA repair and perhaps also replication [].Bacterial primosomal protein N' (PriA). PriA protein is one of sevenproteins that make up the restart primosome, an apparatus that promotesassembly of replisomes at recombination intermediates and stalledreplication forks.Bacterial ATP-dependent DNA helicase recG. It has a critical role inrecombination and DNA repair, helping process Holliday junctionintermediates to mature products by catalyzing branch migration. It has aDNA unwinding activity characteristic of helicases with a 3' to 5'polarity.A variety of DNA and RNA virus helicases and transcription factorsThis entry includes bacterial DinG and eukaryotic Rad3 proteins, differing from other SF1 and SF2 helicases by the presence of a large insert after the Walker A motif [].
SecA is a cytoplasmic protein of 800 to 960 amino acid residues. The eubacterial secA protein []plays an important role in protein export. It interacts with the secY and secE components of the protein translocation system. It has a central role in coupling the hydrolysis of ATP to the transfer of proteins across the membrane.SecA is a superfamily 2 (SF2) helicase that adapted to translocate proteins. It contains the characteristic DEAD/DEXH ATPase core structure with the seven SF2 motifs []. Several structural analyses on secA have been reported [, ]. They show that secA contains two recA-like domains similar to SF1 and SF2 helicases. In helicases, the two recA-like domains move relative to one another during the ATPase cycle, generating domain movements that translocate the helicase along nucleic acids. In secA, it seems that a similar mechanism is used to generate domain movements that are coupled to polypeptide translocation. The N-terminal recA-like domain of secA contains an insert of about 150 residues that forms the preprotein crosslinking domain (PPXD) which has the ability to bind preproteins in solution and which is important for preprotein loading onto SecYEG-containing membranes [].Homologs of secA are also encoded in the chloroplast genome of some algae []as well as in the nuclear genome of plants []. It could be involved in the intraorganellar protein transport into thylakoids.
Helicase nonstructural protein 13 (NSP13) is encoded by the replicase polyprotein 1a/ab of coronaviruses and released after a proteolytic process. It plays a vital role in catalysing the unwinding of duplex oligonucleotides into single strands in an NTP-dependent manner. It is a multidomain protein which includes an N-terminal Cys/His rich zinc-binding domain (ZBD), followed by a stalk and 1B domains, and a helicase core that belongs to the superfamily SF1 of helicases, containing two RecA1 and RecA2 domains [, ]. The stalk region connects the ZBD domain and 1B domain. Nsp13 adopts a triangular pyramid shape in which the two RecA1 and A2 and 1B domain form the triangular base, while N-terminal ZBD and stalk domains are arranged at the apex of the pyramid [, , ]. Recently, it has been reported that SARS-CoV-2 NSP13 as an interferon antagonist. It is involved in type I interferon (IFN-I) response as it binds and blocks TBK1 phosphorylation to inhibit interferon regulatory factor 3 (IRF3) which results in decreased IRF3 activation [, ].This entry represents the 1B domain, which has a regulatory role modulating the nucleic acid substrate binding. Based on the structures from the related Equine arteritis virus (EAV) NSP10, it is likely that 1B domain forms a channel together with 1A and 2A domains that accommodates the single stranded nucleic acids [, ].
Helicases have been classified in 5 superfamilies (SF1-SF5). All of theproteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. Superfamily 3 consists of helicasesencoded mainly by small DNA viruses and some large nucleocytoplasmic DNAviruses [, ]. Small viruses are very dependent on the host-cell machinery toreplicate. SF3 helicase in small viruses is associated with an origin-bindingdomain. By pairing a domain that recognises the ori with a helicase, the viruscan bypass the host-cell-based regulation pathway and initiate its ownreplication. The protein binds to the viral ori leading to origin unwinding.Cellular replication proteins are then recruited to the ori and the viral DNAis replicated.In SF3 helicases the Walker A and Walker B motifs are separated by spacers ofrather uniform, and relatively short, length. In addition to the A and Bmotifs this family is characterised by a third motif (C) which resides betweenthe B motif and the C terminus of the conserved region. This motif consists ofan Asn residue preceded by a run of hydrophobic residues [].Several structures of SF3 helicases have been solved []. Theyall possess the same core alpha/beta fold, consisting of a five-strandedparallel beta sheet flanked on both sides by several alpha helices. Incontrast to SF1 and SF2 helicases, which have RecA-like core folds, the strandconnectivity within the alpha/beta core domain is that of AAA+ proteins [].The SF3 helicase proteins assemble into a hexameric ring.Some proteins known to contain an SF3 helicase domain are listed below:Polyomavirus large T antigen. It initiates DNA unwinding and replicationvia interactions with the viral origin of replication.Papillomavirus E1 protein. An ATP-dependent DNA helicase required forinitiation of viral DNA replication.Parvovirus Rep/NS1 protein, which is also required for the initiation ofviral replication.Poxviridae and other large DNA viruses D5 protein.Bacteriophage DNA primase/helicase protein.Bacterial prophage DNA primase/helicase protein.The entry represents the core alpha/beta fold of the SF3 helicase domain found predominantly in DNA viruses.
RNA helicases from the DEAD-box family are found in almost all organisms andhave important roles in RNA metabolism such as splicing, RNA transport,ribosome biogenesis, translation and RNA decay. They are enzymes that unwinddouble-stranded RNA molecules in an energy dependent fashion through thehydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) ofhelicases. As other SF1 and SF2 members they contain seven conserved motifswhich are characteristic of these two superfamilies [].DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-bindingaspartic acid). Besides these seven motifs, DEAD-box RNA helicases contain aconserved cluster of nine amino-acids (the Q motif) with an invariantglutamine located N-terminally of motif I. An additional highly conserved butisolated aromatic residue is also found upstream of these nine residues [].The Q motif is characteristic of and unique to DEAD box family of helicases.It is supposed to control ATP binding and hydrolysis, and therefore itrepresents a potential mechanism for regulating helicase activity.Several structural analyses of DEAD-box RNA helicases have been reported [, ]. The Q motif is located in close proximity to motif I. Theconserved glutamine and aromatic residues interact with the ADP molecule.Some proteins known to contain a Q motif:Eukaryotic initiation factor 4A (eIF4A). An ATP-dependent RNA helicasewhich is a subunit of the eIF4F complex involved in cap recognition andrequired for mRNA binding to ribosome.Various eukaryotic helicases involved in ribosome biogenesis (DBP3, DRS1,SPB4, MAK5, DBP6, DBP7, DBP9, DBP10).Eukaryotic DEAD-box proteins involved in pre-mRNA splicing (Prp5p, Prp28pand Sub2p).DEAD-box proteins required for mitochondrial genome expression (MSS116 andMRH4).Fungi ATP-dependent RNA helicase DHH1. It is required for decapping andturnover of mRNA.Fungi ATP-dependent RNA helicase DBP5. It is involved in nucleo-cytoplasmictransport of poly(A) RNA.Bacterial ATP-dependent RNA helicase rhlB. It is involved in the RNAdegradosome, a multi-enzyme complex important in RNA processing andmessenger RNA degradation.Bacterial cold-shock DEAD box protein A.This entry represents a region stretching from the conserved aromatic residue to one amino acid after the glutamine of the Q motif.
Helicases have been classified in 5 superfamilies (SF1-SF5). All of theproteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. Superfamily 3 consists of helicasesencoded mainly by small DNA viruses and some large nucleocytoplasmic DNAviruses [, ]. Small viruses are very dependent on the host-cell machinery toreplicate. SF3 helicase in small viruses is associated with an origin-bindingdomain. By pairing a domain that recognises the ori with a helicase, the viruscan bypass the host-cell-based regulation pathway and initiate its ownreplication. The protein binds to the viral ori leading to origin unwinding.Cellular replication proteins are then recruited to the ori and the viral DNAis replicated.In SF3 helicases the Walker A and Walker B motifs are separated by spacers ofrather uniform, and relatively short, length. In addition to the A and Bmotifs this family is characterised by a third motif (C) which resides betweenthe B motif and the C terminus of the conserved region. This motif consists ofan Asn residue preceded by a run of hydrophobic residues [].Several structures of SF3 helicases have been solved []. Theyall possess the same core alpha/beta fold, consisting of a five-strandedparallel beta sheet flanked on both sides by several alpha helices. Incontrast to SF1 and SF2 helicases, which have RecA-like core folds, the strandconnectivity within the alpha/beta core domain is that of AAA+ proteins [].The SF3 helicase proteins assemble into a hexameric ring.Some proteins known to contain an SF3 helicase domain are listed below:Polyomavirus large T antigen. It initiates DNA unwinding and replicationvia interactions with the viral origin of replication.Papillomavirus E1 protein. An ATP-dependent DNA helicase required forinitiation of viral DNA replication.Parvovirus Rep/NS1 protein, which is also required for the initiation ofviral replication.Poxviridae and other large DNA viruses D5 protein.Bacteriophage DNA primase/helicase protein.Bacterial prophage DNA primase/helicase protein.The entry represents the core alpha/beta fold of the SF3 helicase domain from predominantly single-stranded RNA viruses.
Helicases have been classified in 5 superfamilies (SF1-SF5). All of theproteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. Superfamily 3consists of helicasesencoded mainly by small DNA viruses and some large nucleocytoplasmic DNAviruses [, ]. Small viruses are very dependent on the host-cell machinery toreplicate. SF3 helicase in small viruses is associated with an origin-bindingdomain. By pairing a domain that recognises the ori with a helicase, the viruscan bypass the host-cell-based regulation pathway and initiate its ownreplication. The protein binds to the viral ori leading to origin unwinding.Cellular replication proteins are then recruited to the ori and the viral DNAis replicated.In SF3 helicases the Walker A and Walker B motifs are separated by spacers ofrather uniform, and relatively short, length. In addition to the A and Bmotifs this family is characterised by a third motif (C) which resides betweenthe B motif and the C terminus of the conserved region. This motif consists ofan Asn residue preceded by a run of hydrophobic residues [].Several structures of SF3 helicases have been solved []. Theyall possess the same core alpha/beta fold, consisting of a five-strandedparallel beta sheet flanked on both sides by several alpha helices. Incontrast to SF1 and SF2 helicases, which have RecA-like core folds, the strandconnectivity within the alpha/beta core domain is that of AAA+ proteins [].The SF3 helicase proteins assemble into a hexameric ring.Some proteins known to contain an SF3 helicase domain are listed below:Polyomavirus large T antigen. It initiates DNA unwinding and replicationvia interactions with the viral origin of replication.Papillomavirus E1 protein. An ATP-dependent DNA helicase required forinitiation of viral DNA replication.Parvovirus Rep/NS1 protein, which is also required for the initiation ofviral replication.Poxviridae and other large DNA viruses D5 protein.Bacteriophage DNA primase/helicase protein.Bacterial prophage DNA primase/helicase protein.The entry represents the core alpha/beta fold of the SF3 helicase domain found predominantly in DNA viruses.
Helicases have been classified in 5 superfamilies (SF1-SF5). All of theproteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. For the two largest groups, commonlyreferred to as SF1 and SF2, a total of seven characteristic motifs have beenidentified []which are distributed over two structural domains, anN-terminal ATP-binding domain and a C-terminal domain. UvrD-like DNA helicasesbelong toSF1, but they differ from classical SF1/SF2 by alarge insertion in each domain. UvrD-like DNA helicases unwind DNA with a3'-5' polarity [].Crystal structures of several uvrD-like DNA helicases have been solved [, , ]. They are monomeric enzymes consisting of twodomains with a common α-β RecA-like core. The ATP-binding site issituated in a cleft between the N terminus of the ATP-binding domain and thebeginning of the C-terminal domain. The enzyme crystallizes in two differentconformations (open and closed). The conformational difference between the twoforms comprises a large rotation of the end of the C-terminal domain byapproximately 130 degrees. This "domain swiveling"was proposed to be an importantaspect of the mechanism of the enzyme [].Some proteins that belong to the UvrD-like DNA helicase family are listedbelow:Bacterial UvrD helicase. It is involved in the post-incision events ofnucleotide excision repair and methyl-directed mismatch repair. It unwindsDNA duplexes with 3'-5' polarity with respect to the bound strand andinitiates unwinding most effectively when a single-stranded region ispresent.Gram-positive bacterial pcrA helicase, an essential enzyme involved in DNArepair and rolling circle replication. The Staphylococcus aureus pcrAhelicase has both 5'-3' and 3'-5' helicase activities.Bacterial rep proteins, a single-stranded DNA-dependent ATPase involved inDNA replication which can initiate unwinding at a nick in the DNA. It bindsto the single-stranded DNA and acts in a progressive fashion along the DNAin the 3' to 5' direction.Bacterial helicase IV (helD gene product). It catalyzes the unwinding ofduplex DNA in the 3'-5' direction.Bacterial recB protein. RecBCD is a multi-functional enzyme complex thatprocesses DNA ends resulting from a double-strand break. RecB is a helicasewith a 3'-5' directionality.Fungal srs2 proteins, an ATP-dependent DNA helicase involved in DNA repair. The polarity of the helicase activity was determined to be 3'-5'.This domain is also found bacterial helicase-nuclease complex AddAB, both in subunit AddA and AddB. The AddA subunit is responsable for the helicase activity. AddB also harbors a putative ATP-binding domain which does not play a role as a secondary DNA motor, but that it may instead facilitate the recognition of the recombination hotspot sequences [].This entry represents the ATP-binding domain found in AddA, AddB and UvrD-like helicases.
Helicases have been classified in 5 superfamilies (SF1-SF5) []. All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop), and Walker B (Mg2+-binding aspartic acid) motifs []. For the two largest groups, commonly referred to as SF1 and SF2, a total of seven characteristic motifs have been identified []which are distributed over two structural domains, an N-terminal ATP-binding domain and a C-terminal domain.This entry represents the C-terminal domain.UvrD-like DNA helicases belong to SF1, but they differ from classical SF1/SF2 by a large insertion in each domain. UvrD-like DNA helicases unwind DNA with a 3'-5' polarity []. Crystal structures of several uvrD-like DNA helicases have been solved [, , ]. They are monomeric enzymes consisting of two domains with a common α-β RecA-like core. The ATP-binding site is situated in a cleft between the N terminus of the ATP-binding domain and the beginning of the C-terminal domain. The enzyme crystallizes in two different conformations (open and closed). The conformational difference between the two forms comprises a large rotation of the end of the C-terminal domain by approximately 130 degrees. This "domain swiveling"was proposed to be an important aspect of the mechanism of the enzyme [].Some proteins that belong to the uvrD-like DNA helicase family are listed below:Bacterial UvrD helicase. It is involved in the post-incision events of nucleotide excision repair and methyl-directed mismatch repair. It unwinds DNA duplexes with 3'-5' polarity with respect to the bound strand and initiates unwinding most effectively when a single-stranded region is present.Gram-positive bacterial pcrA helicase, an essential enzyme involved in DNA repair and rolling circle replication. The Staphylococcus aureus pcrA helicase has both 5'-3' and 3'-5' helicase activities. Bacterial rep proteins, a single-stranded DNA-dependent ATPase involved in DNA replication which can initiate unwinding at a nick in the DNA. It binds to the single-stranded DNA and acts in a progressive fashion along the DNA in the 3' to 5' direction.Bacterial helicase IV (helD gene product). It catalyzes the unwinding of duplex DNA in the 3'-5' direction.Bacterial recB protein. RecBCD is a multi-functional enzyme complex that processes DNA ends resulting from a double-strand break. RecB is a helicase with a 3'-5' directionality.Fungal srs2 proteins, an ATP-dependent DNA helicase involved in DNA repair. The polarity of the helicase activity was determined to be 3'-5'.
