PT  - JOURNAL ARTICLE
AU  - Xu, Cong
AU  - Wang, Yanxing
AU  - Liu, Caixuan
AU  - Zhang, Chao
AU  - Han, Wenyu
AU  - Hong, Xiaoyu
AU  - Wang, Yifan
AU  - Hong, Qin
AU  - Wang, Shutian
AU  - Zhao, Qiaoyu
AU  - Wang, Yalei
AU  - Yang, Yong
AU  - Chen, Kaijian
AU  - Zheng, Wei
AU  - Kong, Liangliang
AU  - Wang, Fangfang
AU  - Zuo, Qinyu
AU  - Huang, Zhong
AU  - Cong, Yao
TI  - Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM
AID  - 10.1126/sciadv.abe5575
DP  - 2021 Jan 01
TA  - Science Advances
PG  - eabe5575
VI  - 7
IP  - 1
4099  - http://advances.sciencemag.org/content/7/1/eabe5575.short
4100  - http://advances.sciencemag.org/content/7/1/eabe5575.full
SO  - Sci Adv2021 Jan 01; 7
AB  - 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.