Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1.
Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1.
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DOI：
10.1016/j.cell.2022.06.023
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发表时间：
2022-08-04
期刊：
影响因子：
64.5
通讯作者：
Gao, George Fu
中科院分区：
文献类型：
--
作者：
Li, Linjie;Liao, Hanyi;Meng, Yumin;Li, Weiwei;Han, Pengcheng;Liu, Kefang;Wang, Qing;Li, Dedong;Zhang, Yanfang;Wang, Liang;Fan, Zheng;Zhang, Yuqin;Wang, Qiyue;Zhao, Xin;Sun, Yeping;Huang, Niu;Qi, Jianxun;Gao, George Fu
目前流行的Omicron亚变体是SARS-CoV-2菌株，具有最多的已知突变。在此，我们发现人血管紧张素转换酶2（hACE 2）与四种早期Omicron亚变体（BA.1、BA.1.1、BA.2和BA.3）的受体结合结构域（RBD）的结合亲和力遵循BA.1.1 > BA.2 > BA.3> BA.1的顺序。hACE 2与BA.1.1、BA.2和BA.3的RBD的复合物结构揭示，BA.2比BA.1的hACE 2结合亲和力更高与BA.2中不存在G496 S突变有关。BA.1.1中的R346 K突变通过长程改变主要影响BA.1.1 RBD/hACE 2界面中的相互作用网络，并导致BA.1.1 RBD的hACE 2亲和力高于BA.1 RBD。这些结果揭示了BA.1.1、BA.2和BA.3 RBD之间不同hACE 2结合模式的结构基础。对人血管紧张素转换酶-2（ACE 2，SARS-CoV-2病毒进入的受体）和四种Omicron亚变体-BA.1，BA.1.1，BA.2和BA.3的受体结合结构域（RBD）的生化和结构分析有助于揭示亚变体结合亲和力差异的结构基础和RBD突变的影响。
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 receptor-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 ≈ 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. The biochemical and structural analysis of the human angiotensin-converting enzyme-2 (ACE2, the receptor for SARS-CoV-2 viral entry) and the receptor-binding domain (RBD) of four Omicron sub-variants—BA.1, BA.1.1, BA.2, and BA.3—helps to reveal the structural basis of differences in sub-variant binding affinities and the impact of RBD mutations.
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DOI：
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发表时间：
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影响因子：
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DOI：
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Acta crystallographica. Section D, Biological crystallography
影响因子：
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