Nucleic Acid Helicases and Translocases.PDF

888 Cell 134,September 5,2008 2008 Elsevier Inc.DOI 10.1016/j.cell.2008.08.027See online version for table legend,abbreviations,and references.SnapShot:Nucleic Acid Helicases and TranslocasesJames M.BergerCalifornia Institute for Quantitative Biology,University of California Berkeley,Berkeley,CA 94720,USA superfamily/classProtein foldoligomeric statePolarityfunction example membersHelicasesSuperfamily I(SF-I)RecA(tandem pair)Monomer(dimer/multimer)3-5(SF-IA),5-3(SF-IB)DNA unwinding,repair and degradationBacterial PcrA,Rep,UvrD,RecBCD,Dda;eukaryotic Rrm3,Pif1,Dna2Superfamily II(SF-II)RecA(tandem pair)Monomer(dimer/multimer)3-5(SF-IIA),5-3(SF-IIB),some dsDNA translocasesRNA melting,RNA-binding protein displacement;DNA or RNA unwinding;chromatin remodeling;DNA/RNA translocation;melting and migration of Holliday junctions or branched structuresDExD/H-box proteins(eukaryotic eIF4A,Prp2,Ski2,Vasa,Dpbs,NS3 of hepatitis C);Snf2/SWI proteins(eukaryotic Snf2,ISWI,Rad54,archaeal Hel308);bacterial RecQ,RecG,UvrBSuperfamily III(SF-III)AAA+Hexamer(dodecamer?)3-5DNA unwinding/replicationPapilloma virus E1,simian virus 40 Large T-antigen,adeno-associated virus Rep40Superfamily IV(SF-IV)RecAHexamer(other states?)5-3(dsDNA?)DNA unwinding/replication;ssRNA packaging Bacterial DnaB;phage T7 gp4,T4 gp41,SPP1 G40P;pRSF1010 RepA;phage 12 P4;mitochondrial protein TwinkleSuperfamily V(SF-V)RecAHexamer5-3RNA translocation,RNA/DNA heteroduplex unwinding;transcription termination Bacterial RhoSuperfamily VI(SF-VI)AAA+(PS-II clade)Hexamer(other states?)3-5(dsDNA?)DNA unwinding/replicationEukaryotic/archaeal MCMsSuperfamily VII?(SF-VII)AAA+(new clade?)Hexamer5-3Chromatin remodeling Eukaryotic Tip48/49,Reptin/pontintranslocasesHerA/FtsKRecA-likeHexamer(pentamer)dsDNA or ssDNAChromosome partitioning/conjugation;certain viral packaging motorsBacterial FtsK,SpoIIIE;plasmid TrwB,TraD;podovirus 29 gp16,caudovirus and herpesvirus terminase proteinsRuvBAAA+(HCLR clade)Hexamer(dodecamer with RuvA protein)dsDNABranch migrationBacterial RuvBMcrBAAA+(H2-insert clade)HeptamerdsDNAType IV restriction enzymesBacterial McrBfigure legend:topology diagrams of Helicases and translocasesThe RecA and AAA+folds are built from an ancestral ASCE domain(turquoise).The relative position of bound nucleotide is shown,and certain nucleoside-triphosphate binding motifs are highlighted(sensor I;sensor II;arginine-fi nger;Walker-A and Walker-B motifs).The catalytic glutamic acid of the Walker-B motif can occupy alternative positions in some subfamilies(pale red spheres).The AAA+sensor-I amino acid is generally a polar residue that is also found in other ASCE proteins.Triangles represent common insertion points for domains or secondary structural elements that are specifi c to select helicase and translocase groups(e.g.,domains IB and IIB of SF-I helicases,or the pre-sensor I hairpin of AAA+proteins).The diverse placement of arginine fi nger elements arises from distinct tertiary and quaternary arrangements of domains or subunits in different subfamilies.888.e1 Cell 134,September 5,2008 2008 Elsevier Inc.DOI 10.1016/j.cell.2008.08.027SnapShot:Nucleic Acid Helicases and TranslocasesJames M.BergerCalifornia Institute for Quantitative Biology,University of California Berkeley,Berkeley,CA 94720,USATable LegendHelicase and translocase proteins constitute a family of nucleic acid-dependent molecular motors that consume nucleoside triphosphates(typically ATP)as fuel for directed movement along nucleic acid.Translocases track along a DNA or RNA substrate to move nucleic acid to a different location or to clear the nucleic acid of proteins.Helicases also move along nucleic acid,but in addition further separate the paired strands.The action of these motors is required for a host of essential cellular transactions,including DNA replication,DNA recombination and repair,the regulation of gene transcription,mRNA maturation and export,translation,and chromosome partitioning and packaging.All helicases and translocases contain one of two catalytic NTP-binding domains:the RecA fold and the AAA+fold(see Figure).These two folds are themselves predicated on an ancestral domain termed an ASCE fold,which is distantly related to classic P loop NTPase folds found in adenylate kinase and G proteins.Within the AAA+fam-ily of helicases and translocases,there are multiple subgroups(clades)defined by distinct insertions to the core AAA+fold.For example,AAA+helicases and translocases belong to the following clades:Superfamily III(SF-III),pre-sensor II(PS-II)clade,HCLR(HslU,Clp,Lon,RuvB)clade,and Helix-2(H2)insert clade.Helicases of the SF-I and SF-II groups(e.g.,PcrA,eIF4A,RecQ)unwind nucleic acids or move along nucleic acid strands as monomers but may also participate in higher-order oligomeric complexes.Helicases belonging to SF-III through SF-VII groups(e.g.,DnaB,SV40 large T antigen,Rho,MCMs)act predominantly as hexamers,although heptamers,dodecamers,tet-radecamers,and even helical filaments have been observed.Many phage packaging motors belong to a diverging branch of the HerA/FtsK family of bacterial translocases and are pentamers.Although SF-IV helicases may work as 3-5 single-stranded DNA unwindases(or 3-5 RNA-packaging motors),double-stranded(ds)DNA translocation activity has been reported for proteins such as DnaB and T7 gp4.The preferred substrate for SF-VI helicases(MCMs)is still under debate.Helicases of the Tip48/49 family have been described as RuvB-like and related to classic AAA+ATPases such as NSF,Cdc48(p97),and FtsH.However,their core ATP-binding subunit does not contain a hairpin insertion prior to the sensor I motif,as is the case for RuvB,but instead has an extended sheet capped by an OB-fold.The AAA+fold in the Tip48/49 eukaryotic helicases also contains a hairpin in place of the helix that connects the penultimate and final strands of the core fold;this insertion is unique among AAA+ATPases.Functionally,the primary activity of RuvB is to translocate dsDNA across the RuvA tetramer to promote branch migration.Tip48/49 helicases,in contrast,display direct DNA-unwinding activity,and may therefore constitute a distinct clade of AAA+proteins.The HerA/FtsK group of bacterial translocases is an offshoot of the RecA family(particularly SF-IV helicases).These enzymes are also structural homologs of other translocases such as PilT and VirB of bacterial type IV secretory systems.AbbreviationsAAA+,ATPases associated with various cellular activities;ASCE,additional strand conserved E;dsDNA,double-stranded DNA;MCMs,minichromosomal maintenance proteins;NSF,N-ethyl maleimide-sensitive factor;NTP,nucleoside triphosphate;OB-fold,oligonucleotide/oligosaccharide binding fold;PS-II,pre-sensor II;ssRNA,single-stranded RNA.AcknowledgmentsJ.M.B.is supported by NIGMS(GM071747).RefeRencesBurroughs,A.M.,Iyer,L.M.,and Aravind,L.(2007).Comparative Genomics and Evolutionary Trajectories of Viral ATP Dependent DNA-Packaging Systems.Gene and Protein Evolution 3,4865.Durr,H.,Flaus,A.,Owen-Hughes,T.,and Hopfner,K.P.(2006).Snf2 family ATPases and DExx box helicases:differences and unifying concepts from high-resolution crystal structures.Nucleic Acids Res.34,41604167.Enemark,E.J.,and Joshua-Tor,L.(2008).On helicases and other motor proteins.Curr.Opin.Struct.Biol.18,243257.Erzberger,J.P.,and Berger,J.M.(2006).Evolutionary relationships and structural mechanisms of AAA+proteins.Annu.Rev.Biophys.Biomol.Struct.35,93114.Gallant,P.(2007).Control of transcription by Pontin and Reptin.Trends Cell Biol.17,187192.Lohman,T.M.,Tomko,E.J.,and Wu,C.G.(2008).Non-hexameric DNA helicases and translocases:mechanisms and regulation.Nat.Rev.Mol.Cell Biol.9,391401.Mackintosh,S.G.,and Raney,K.D.(2006).DNA unwinding and protein displacement by superfamily 1 and superfamily 2 helicases.Nucleic Acids Res.34,41544159.Patel,S.S.,and Donmez,I.(2006).Mechanisms of helicases.J.Biol.Chem.281,1826518268.Pyle,A.M.(2008).Translocation and unwinding mechanisms of RNA and DNA helicases.Annu.Rev.Biophys.37,317336.Singleton,M.R.,Dillingham,M.S.,and Wigley,D.B.(2007).Structure and mechanism of helicases and nucleic acid translocases.Annu.Rev.Biochem.76,2350.