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Fido, a Novel AMPylation Domain Common to Fic, Doc, and AvrB 英文参考文献
Fido,aNovelAMPylationDomainCommontoFic,Doc,
andAvrB
LisaN.Kinch1*,MelanieL.Yarbrough3,KimOrth3,NickV.Grishin1,2
1HowardHughesMedicalInstitute,UniversityofTexasSouthwesternMedicalCenter,Dallas,Texas,UnitedStatesofAmerica,2DepartmentofBiochemistry,Universityof
TexasSouthwesternMedicalCenter,Dallas,Texas,UnitedStatesofAmerica,3DepartmentofMolecularBiology,UniversityofTexasSouthwesternMedicalCenter,Dallas,
Texas,UnitedStatesofAmerica
Abstract
Background:TheVibrioparahaemolyticustypeIIIsecretedeffectorVopScontainsaficdomainthatcovalentlymodifiesRho
GTPasethreoninewithAMPtoinhibitdownstreamsignalingeventsinhostcells.TheVopSficdomainincludesaconserved
sequencemotif(HPFx[D/E]GN[G/K]R)thatcontributestoAMPylation.Ficdomainsarefoundinavarietyofspecies,including
bacteria,afewarchaea,andmetazoaneukaryotes.
Methodology/PrincipalFindings:WeshowthattheAMPylationactivityextendstoaeukaryoticficdomaininDrosophila
melanogasterCG9523,andusesequenceandstructurebasedcomputationalmethodstoidentifyrelateddomainsindoc
toxins and the type III effector AvrB. The conserved sequence motif that contributes to AMPylation unites fic with doc.
Although AvrB lacks this motif, its structure reveals a similar topology to the fic and doc folds. AvrB binds to a peptide
fragmentofitshostvirulencetargetinasimilarmannerasficbindspeptidesubstrate.AvrBalsoorientsaphosphategroup
fromaboundADPligandnearthepeptide-bindingsiteandinasimilarpositionasaboundficphosphate.
Conclusions/Significance:ThedemonstratedeukaryoticficdomainAMPylationactivitysuggeststhattheVopSeffectorhas
exploitedanovelhostposttranslationalmodification.Ficdomain-relatedstructuresgiveinsighttotheAMPylationactive
siteandtotheVopSficdomaininteractionwithitshostGTPasetarget.Theseresultssuggestthatfic,doc,andAvrBstem
fromacommonancestorthathasevolvedtoAMPylateproteinsubstrates.
Citation:KinchLN,YarbroughML,OrthK,GrishinNV(2009)Fido,aNovelAMPylationDomainCommontoFic,Doc,andAvrB.PLoSONE4(6):e5818.doi:10.1371/
journal.pone.0005818
Editor:BostjanKobe
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