The R Protein of SARS-CoV: Analyses of Structure and Function Based on Four Complete Genome Sequences of Isolates BJ01-BJ04

(整期优先)网络出版时间:2003-02-12
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TheR(replicase)proteinistheuniquelydefinednon-structuralprotein(NSP)responsibleforRNAreplication,mutationrateorfidelity,regulationoftranscrip-tionincoronavirusesandmanyotherssRNAviruses.Basedonourcompletegenomesequencesoffourisolates(BJ01-BJ04)ofSARS-CoVfromBeijing,China,weanalyzedthestructureandpredictedfunctionsoftheRproteinincomparisonwith13otherisolatesofSARS-CoVand6othercoronaviruses.TheentireORF(open-readingframe)encodesfortwomajorenzymeactivities,RNA-dependentRNApolymerase(RdRp)andproteinaseactivities.TheRpolyproteinunder-goesacomplexproteolyticprocesstoproduce15function-relatedpeptides.Ahydrophobicdomain(HOD)andahydrophilicdomain(HID)arenewlyidentifiedwithinNSP1.ThesubstitutionrateoftheRproteinisclosetotheaverageoftheSARS-CoVgenome.ThefunctionaldomainsinallNSPsoftheRproteingivedifferentphylogeneticresultsthatsuggesttheirdifferentmutationrateunderselectivepressure.ElevenhighlyconservedregionsinRdRpandtwelvecleavagesitesby3CLP(chymotrypsin-likeprotein)havebeenidentifiedaspotentialdrugtargets.Findingssuggestthatitispossibletoobtaininformationaboutthephy-logenyofSARS-CoV,aswellaspotentialtoolsfordrugdesign,genotypinganddiagnosticsofSARS.