The R protein of SARS-CoV: analyses of structure and function based on four complete genome sequences of isolates BJ01-BJ04.
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.
Xu
Zuyuan
Z
Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300, China.
Zhang
Haiqing
H
Tian
Xiangjun
X
Ji
Jia
J
Li
Wei
W
Li
Yan
Y
Tian
Wei
W
Han
Yujun
Y
Wang
Lili
L
Zhang
Zizhang
Z
Xu
Jing
J
Wei
Wei
W
Zhu
Jingui
J
Sun
Haiyan
H
Zhang
Xiaowei
X
Zhou
Jun
J
Li
Songgang
S
Wang
Jun
J
Wang
Jian
J
Bi
Shengli
S
Yang
Huanming
H
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
D012324:RNA-Dependent RNA Polymerase