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SARS-CoV-2 S trimer, S-closed
Structural highlights
Publication Abstract from PubMedThe recent outbreaks and rapid international spread of SARS-CoV-2 pose a global health emergency. Its trimeric spike (S) glycoprotein interacts with human ACE2-receptor to mediate viral entry into host-cells. Here we present 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 A and 3.8 A resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing-motions within the S-trimer. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer regarding receptor-triggered transformation from the closed prefusion state to 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 ground prefusion state toward postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM.,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 Sci Adv. 2020 Dec 4. pii: sciadv.abe5575. doi: 10.1126/sciadv.abe5575. PMID:33277323[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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