Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies.
Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies.
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SARS-CoV-2 Delta 变体识别 ACE2 受体和广泛中和抗体的结构基础
DOI：
10.1038/s41467-022-28528-w
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发表时间：
2022-02-15
影响因子：
16.6
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Wang Y;Liu C;Zhang C;Wang Y;Hong Q;Xu S;Li Z;Yang Y;Huang Z;Cong Y
The SARS-CoV-2 Delta variant is currently the dominant circulating strain in the world. Uncovering the structural basis of the enhanced transmission and altered immune sensitivity of Delta is particularly important. Here we present cryo-EM structures revealing two conformational states of Delta spike and S/ACE2 complex in four states. Our cryo-EM analysis suggests that RBD destabilizations lead to population shift towards the more RBD-up and S1 destabilized fusion-prone state, beneficial for engagement with ACE2 and shedding of S1. Noteworthy, we find the Delta T478K substitution plays a vital role in stabilizing and reshaping the RBM loop473-490, enhancing interaction with ACE2. Collectively, increased propensity for more RBD-up states and the affinity-enhancing T478K substitution together contribute to increased ACE2 binding, providing structural basis of rapid spread of Delta. Moreover, we identify a previously generated MAb 8D3 as a cross-variant broadly neutralizing antibody and reveal that 8D3 binding induces a large K478 side-chain orientation change, suggesting 8D3 may use an “induced-fit” mechanism to tolerate Delta T478K mutation. We also find that all five RBD-targeting MAbs tested remain effective on Delta, suggesting that Delta well preserves the neutralizing antigenic landscape in RBD. Our findings shed new lights on the pathogenicity and antibody neutralization of Delta.
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SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
DOI：
10.1016/j.str.2021.05.014
发表时间：
2021-07-01
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Cerutti G;Rapp M;Guo Y;Bahna F;Bimela J;Reddem ER;Yu J;Wang P;Liu L;Huang Y;Ho DD;Kwong PD;Sheng Z;Shapiro L
通讯作者：
Shapiro L
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
1.6
作者：
Gao, Qijun;Hu, Yingfu;Wu, Jing
通讯作者：
Wu, Jing