Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM.
Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM.
复制标题
冷冻电子显微镜研究SARS-CoV-2三聚体刺突糖蛋白与ACE2受体结合的构象动力学
DOI：
10.1126/sciadv.abe5575
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Xu C;Wang Y;Liu C;Zhang C;Han W;Hong X;Wang Y;Hong Q;Wang S;Zhao Q;Wang Y;Yang Y;Chen K;Zheng W;Kong L;Wang F;Zuo Q;Huang Z;Cong Y
Structure of SARS-CoV-2 spike in complex with ACE2 reveals the mechanism of ACE2 induced spike conformational transitions. The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti–SARS-CoV-2 vaccines and therapeutics.
