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TitleConformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM.
Journal, issue, pagesSci Adv, Vol. 7, Issue 1, Year 2021
Publish dateJan 1, 2021
AuthorsCong Xu / Yanxing Wang / Caixuan Liu / Chao Zhang / Wenyu Han / Xiaoyu Hong / Yifan Wang / Qin Hong / Shutian Wang / Qiaoyu Zhao / Yalei Wang / Yong Yang / Kaijian Chen / Wei Zheng / Liangliang Kong / Fangfang Wang / Qinyu Zuo / Zhong Huang / Yao Cong /
PubMed AbstractThe 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 ...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.
External linksSci Adv / PubMed:33277323 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 6.0 Å
Structure data

30660

7df3

EMDB-30660, PDB-7df3:
SARS-CoV-2 S trimer, S-closed
Method: EM (single particle) / Resolution: 2.7 Å

30661

7df4

EMDB-30661, PDB-7df4:
SARS-CoV-2 S-ACE2 complex
Method: EM (single particle) / Resolution: 3.8 Å

30701

7dk3

EMDB-30701, PDB-7dk3:
SARS-CoV-2 S trimer, S-open
Method: EM (single particle) / Resolution: 6.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Spike glycoprotein / coronavirus / SARS-CoV-2 virus / closed state / receptor ACE2 / COVID-19

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