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  • 秦照玲,罗利.严重急性呼吸综合征冠状病毒2主要蛋白质分子的氨基酸变异分析[J].第二军医大学学报,2020,41(5):465-473    [点击复制]
  • QIN Zhao-ling,LUO Li.Analysis of amino acid variations of major proteins from severe acute respiratory syndrome coronavirus 2[J].Acad J Sec Mil Med Univ,2020,41(5):465-473   [点击复制]
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严重急性呼吸综合征冠状病毒2主要蛋白质分子的氨基酸变异分析
秦照玲1,罗利2*
0
(1. 海军军医大学(第二军医大学)海军医学系生物医学防护教研室, 上海 200433;
2. 上海大学生命科学学院, 上海 200444
*通信作者)
摘要:
目的 应用生物物理学方法鉴定分析严重急性呼吸综合征冠状病毒2(SARS-CoV-2)中主要蛋白质分子的关键氨基酸变异。方法 通过氨基酸序列同源比对、突变氨基酸残基分类、蛋白质三维结构重建和氨基酸残基静电相互作用测量,以同源性最高的蝙蝠冠状病毒RaTG13为参照,进行SARS-CoV-2中主要蛋白质分子的关键氨基酸变异分析。结果 初步分析确定SARS-CoV-2中RNA依赖的RNA聚合酶(RdRp)、核糖核酸外切酶(ExoN)、尿苷酸特异性核糖核酸内切酶(NendoU)和刺突蛋白(S蛋白)上至少发生了10处影响静电相互作用的氨基酸变异,这些变异可能影响蛋白质分子的空间构象及其生物学功能。结论 初步确定了SARS-CoV-2中主要蛋白质分子的关键氨基酸变异,为理解SARS-CoV-2的遗传特性、致病性和流行病学特征提供了有用线索。
关键词:  严重急性呼吸综合征冠状病毒2  蛋白质类  氨基酸变异  蛋白质构象  盐键  斥力
DOI:10.16781/j.0258-879x.2020.05.0465
投稿时间:2020-03-25修订日期:2020-04-19
基金项目:
Analysis of amino acid variations of major proteins from severe acute respiratory syndrome coronavirus 2
QIN Zhao-ling1,LUO Li2*
(1. Department of Biomedical Defense, Faculty of Naval Medicine, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. School of Life Sciences, Shanghai University, Shanghai 200444, China
*Corresponding author)
Abstract:
Objective To identify key amino acid variations of major proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by biophysical methods. Methods Through amino acid sequence alignment, classification of variant amino acid residues, three-dimensional structure reconstruction of proteins, and electrostatic interaction analysis of amino acid residues, the key amino acid variations of major proteins from SARS-CoV-2 was analyzed with RaTG13, the bat coronavirus with the highest homology, as the reference. Results At least ten amino acid variations that affect the possible electrostatic interactions were identified in RNA-dependent RNA polymerase (RdRp), exoribonuclease (ExoN), uridylate-specific endoribonuclease (NendoU), and spike (S) protein from SARS-CoV-2. These variations may affect the spatial conformation and biological functions of the proteins. Conclusion The key amino acid variations of the major proteins from SARS-CoV-2 have been preliminarily identified, providing clues for understanding the genetic, pathogenic and epidemiological characteristics of the virus.
Key words:  severe acute respiratory syndrome coronavirus 2  proteins  amino acid variations  protein conformation  salt bond  repulsion