Evolutionary Constraints Acting on DDX3X Protein Potentially Interferes with Rev-Mediated Nuclear Export of HIV-1 RNA 英文参考文献.docVIP

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Evolutionary Constraints Acting on DDX3X Protein Potentially Interferes with Rev-Mediated Nuclear Export of HIV-1 RNA 英文参考文献.doc

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Evolutionary Constraints Acting on DDX3X Protein Potentially Interferes with Rev-Mediated Nuclear Export of HIV-1 RNA 英文参考文献

EvolutionaryConstraintsActingonDDX3XProtein PotentiallyInterfereswithRev-MediatedNuclearExport ofHIV-1RNA DeepakSharma,JayantaBhattacharya* DepartmentofMolecularVirology,NationalAIDSResearchInstitute,IndianCouncilofMedicalResearch,Bhosari,Pune,India Abstract Differentialhost-pathogeninteractionsdirectviralreplicationininfectedcells.InHIV-1infectedcells,nuclearexportofviral RNAtranscriptsintocellularcytoplasmisgovernedbyinteractionofHIV-1Rev,Exportin-1(CRM-1)andDDX3X.Knockdown ofDDX3XhasbeenshowntodrasticallyimpairHIVreplication.Hereweshowthatevolutionaryforcesareresponsiblefor demarkingpreviouslyunidentifiedcriticalfunctionallyimportantresiduesonthesurfaceofDDX3X.Usingcomputational approaches,weshowthatthesefunctionalresidues,dependingontheirlocation,arecapableofregulatingATPaseandRNA helicasefunctionsofDDX3X.ThepotentialoftheseresiduesindesigningbetterblockersagainstHIV-1replicationwasalso assessed. Also, using stepwise docking simulations, we could identify DDX3X-CRM-1 interface and its critical functional residues.OurdatawouldhelpexplaintheroleofDDX3XinHIV-1Revfunctionwithpotentialtodesignnewintervention strategiesagainstHIV-1replication. Citation:SharmaD,BhattacharyaJ(2010)EvolutionaryConstraintsActingonDDX3XProteinPotentiallyInterfereswithRev-MediatedNuclearExportofHIV-1 RNA.PLoSONE5(3):e9613.doi:10.1371/journal.pone.0009613 Editor:WayneDelport,UniversityofCaliforniaSanDiego,UnitedStatesofAmerica ReceivedAugust20,2009;AcceptedFebruary5,2010;PublishedMarch15,2010 Copyright:?2010sharma,Bhattacharya.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Theseauthorshavenosupportorfundingtoreport. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:jbhattacharya@ Introduction computational and evolutionary analysis to analyze evolutionary historyandtodetectputativefunctionalresidu