作者
Yifan Wang, Caixuan Liu, Chao Zhang, Yanxing Wang, Qin Hong, Shiqi Xu, Zuyang Li, Yong Yang, Zhong Huang, Yao Cong
发表日期
2022/2/15
期刊
Nature communications
卷号
13
期号
1
页码范围
871
出版商
Nature Publishing Group UK
简介
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 …
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