S373P Mutation Stabilizes the Receptor-Binding Domain of the Spike Protein in Omicron and Promotes Binding

被引:16
作者
Zheng, Bin [1 ]
Xiao, Yuelong [1 ]
Tong, Bei [2 ]
Mao, Yutong [1 ]
Ge, Rui [1 ]
Tian, Fang [1 ]
Dong, Xianchi [3 ,4 ]
Zheng, Peng [1 ]
机构
[1] Nanjing Univ, Chem & Biomed Innovat Ctr ChemBIC, Sch Chem & Chem Engn, State Key Lab Coordinat Chem, Nanjing 210023, Jiangsu, Peoples R China
[2] Jiangsu Prov & Chinese Acad Sci, Inst Bot, Nanjing 210014, Jiangsu, Peoples R China
[3] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Jiangsu, Peoples R China
[4] Minist Educ, Engn Res Ctr Prot & Peptide Med, Nanjing 210023, Jiangsu, Peoples R China
来源
JACS AU | 2023年 / 3卷 / 07期
基金
中国国家自然科学基金;
关键词
single-molecule force spectroscopy; SARS-CoV-2; Omicron variant; SMD; biophysics; MOLECULE FORCE SPECTROSCOPY; ELASTICITY;
D O I
10.1021/jacsau.3c00142
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A cluster of several newly occurring mutations on Omicronis foundat the & beta;-core region of the spike protein's receptor-bindingdomain (RBD), where mutation rarely happened before. Notably, thebinding of SARS-CoV-2 to human receptor ACE2 via RBD happens in adynamic airway environment, where mechanical force caused by coughingor sneezing occurs. Thus, we used atomic force microscopy-based single-moleculeforce spectroscopy (AFM-SMFS) to measure the stability of RBDs andfound that the mechanical stability of Omicron RBD increased by & SIM;20%compared with the wild type. Molecular dynamics (MD) simulations revealedthat Omicron RBD showed more hydrogen bonds in the & beta;-core regiondue to the closing of the & alpha;-helical motif caused primarily bythe S373P mutation. In addition to a higher unfolding force, we showeda higher dissociation force between Omicron RBD and ACE2. This workreveals the mechanically stabilizing effect of the conserved mutationS373P for Omicron and the possible evolution trend of the & beta;-coreregion of RBD.
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页码:1902 / 1910
页数:9
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