The structural characterization and antigenicity of the S protein of SARS-CoV.
The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.
Li
Jingxiang
J
Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300, China.
Luo
Chunqing
C
Deng
Yajun
Y
Han
Yujun
Y
Tang
Lin
L
Wang
Jing
J
Ji
Jia
J
Ye
Jia
J
Jiang
Fanbo
F
Xu
Zhao
Z
Tong
Wei
W
Wei
Wei
W
Zhang
Qingrun
Q
Li
Shengbin
S
Li
Wei
W
Li
Hongyan
H
Li
Yudong
Y
Dong
Wei
W
Wang
Jian
J
Bi
Shengli
S
Yang
Huanming
H
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D001482:Base Composition; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
D000956:Antigens, Viral; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus