Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1

被引：124

作者：

Li, Linjie ^{[1
,2
]}

Liao, Hanyi ^{[1
,2
]}

Meng, Yumin ^{[1
,2
]}

Li, Weiwei ^{[1
,2
]}

Han, Pengcheng ^{[1
,3
]}

Liu, Kefang ^{[1
]}

Wang, Qing ^{[4
]}

Li, Dedong ^{[1
]}

Zhang, Yanfang ^{[1
]}

Wang, Liang ^{[1
]}

Fan, Zheng ^{[1
]}

Zhang, Yuqin ^{[1
]}

Wang, Qiyue ^{[1
]}

Zhao, Xin ^{[1
]}

Sun, Yeping ^{[1
]}

Huang, Niu ^{[4
,5
]}

Qi, Jianxun ^{[1
,2
]}

Gao, George Fu ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, China Univ Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Southeast Univ, Zhongda Hosp, Sch Med, Nanjing 210009, Peoples R China

[4] Natl Inst Biol Sci, 7 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China

[5] Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res, Beijing 102206, Peoples R China

来源：

CELL | 2022年 / 185卷 / 16期

基金：

中国国家自然科学基金;

关键词：

hACE2; Omicron; RBDs; SARS-CoV-2;

D O I：

10.1016/j.cell.2022.06.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The currently circulating Omicron sub-variants are the SARS-CoV-2 strains with the highest number of known mutations. Herein, we found that human angiotensin-converting enzyme 2 (hACE2) binding affinity to the re-ceptor-binding domains (RBDs) of the four early Omicron sub-variants (BA.1, BA.1.1, BA.2, and BA.3) follows the order BA.1.1 > BA.2 > BA.3 z BA.1. The complex structures of hACE2 with RBDs of BA.1.1, BA.2, and BA.3 reveal that the higher hACE2 binding affinity of BA.2 than BA.1 is related to the absence of the G496S mutation in BA.2. The R346K mutation in BA.1.1 majorly affects the interaction network in the BA.1.1 RBD/hACE2 interface through long-range alterations and contributes to the higher hACE2 affinity of the BA.1.1 RBD than the BA.1 RBD. These results reveal the structural basis for the distinct hACE2 binding patterns among BA.1.1, BA.2, and BA.3 RBDs.

引用

页码：2952 / +

页数：20

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