title: The R protein of SARS-CoV: analyses of structure and function based on four complete genome sequences of isolates BJ01-BJ04.
abstract: The R (replicase) protein is the uniquely defined non-structural protein (NSP) responsible for RNA replication, mutation rate or fidelity, regulation of transcription in coronaviruses and many other ssRNA viruses. Based on our complete genome sequences of four isolates (BJ01-BJ04) of SARS-CoV from Beijing, China, we analyzed the structure and predicted functions of the R protein in comparison with 13 other isolates of SARS-CoV and 6 other coronaviruses. The entire ORF (open-reading frame) encodes for two major enzyme activities, RNA-dependent RNA polymerase (RdRp) and proteinase activities. The R polyprotein undergoes a complex proteolytic process to produce 15 function-related peptides. A hydrophobic domain (HOD) and a hydrophilic domain (HID) are newly identified within NSP1. The substitution rate of the R protein is close to the average of the SARS-CoV genome. The functional domains in all NSPs of the R protein give different phylogenetic results that suggest their different mutation rate under selective pressure. Eleven highly conserved regions in RdRp and twelve cleavage sites by 3CLP (chymotrypsin-like protein) have been identified as potential drug targets. Findings suggest that it is possible to obtain information about the phylogeny of SARS-CoV, as well as potential tools for drug design, genotyping and diagnostics of SARS.
authors.affiliation: Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300, China.
authors.forename: Zuyuan
authors.initials: Z
authors.lastname: Xu
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Tian
authors.forename: Jia
authors.initials: J
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Yujun
authors.initials: Y
authors.lastname: Han
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Zizhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jingui
authors.initials: J
authors.lastname: Zhu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Shengli
authors.initials: S
authors.lastname: Bi
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D001482:Base Composition; D001483:Base Sequence; D016000:Cluster Analysis; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D040461:Gene Components; D016679:Genome, Viral; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D012324:RNA-Dependent RNA Polymerase