七肽重复区
脂质双层融合
生物物理学
膜
病毒进入
融合
病毒包膜
生物
冠状病毒
细胞膜
脂质双层
细胞生物学
化学
肽序列
病毒
生物化学
2019年冠状病毒病(COVID-19)
病毒学
病毒复制
基因
病理
传染病(医学专业)
哲学
医学
疾病
语言学
作者
Sai Chaitanya Chiliveri,John M. Louis,Rodolfo Ghirlando,Ad Bax
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-10-08
卷期号:7 (41)
被引量:27
标识
DOI:10.1126/sciadv.abk2226
摘要
Entry of SARS-CoV-2 into a host cell is mediated by spike, a class I viral fusion protein responsible for merging the viral and host cell membranes. Recent studies have revealed atomic-resolution models for both the postfusion 6-helix bundle (6HB) and the prefusion state of spike. However, a mechanistic understanding of the molecular basis for the intervening structural transition, important for the design of fusion inhibitors, has remained elusive. Using nuclear magnetic resonance spectroscopy and other biophysical methods, we demonstrate the presence of α-helical, membrane-bound, intermediate states of spike’s heptad repeat (HR1 and HR2) domains that are embedded at the lipid-water interface while in a slow dynamic equilibrium with the postfusion 6HB state. These results support a model where the HR domains lower the large energy barrier associated with membrane fusion by destabilizing the host and viral membranes, while 6HB formation actively drives their fusion by forcing physical proximity.
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