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原位结构揭示SARS-CoV-2突刺蛋白的柔性基础
作者:小柯机器人 发布时间:2020/8/20 20:33:20

近日,德国马克斯普朗克研究所Martin Beck等研究人员利用SARS-CoV-2突刺的原位结构分析,揭示了由三个铰链介导的柔性。相关论文于2020年8月18日在线发表在《科学》杂志上。

研究人员结合了低温电子断层扫描、局部断层图平均和分子动力学模拟来对突刺(S)蛋白进行结构分析。与重组S相比,病毒S的糖基化程度更高,且大多以封闭的融合前构象出现。研究人员发现,S的杆结构域包含三个铰链,从而赋予头部的定向自由度。
 
研究人员认为,铰链允许S扫描宿主细胞表面,并被广泛的聚糖涂层所屏蔽。天然S的结构有助于人们对SARS-CoV-2感染和疫苗开发的了解。
 
据悉,SARS-CoV-2的S蛋白是细胞进入所必需的,也是疫苗开发的主要重点。 
 
附:英文原文

Title: In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges

Author: Beata Turoňová, Mateusz Sikora, Christoph Schürmann, Wim J. H. Hagen, Sonja Welsch, Florian E. C. Blanc, Sren von Bülow, Michael Gecht, Katrin Bagola, Cindy Hrner, Ger van Zandbergen, Jonathan Landry, Nayara Trevisan Doimo de Azevedo, Shyamal Mosalaganti, Andre Schwarz, Roberto Covino, Michael D. Mühlebach, Gerhard Hummer, Jacomine Krijnse Locker, Martin Beck

Issue&Volume: 2020/08/18

Abstract: Abstract The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. Here, we combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed pre-fusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines.

DOI: 10.1126/science.abd5223

Source: https://science.sciencemag.org/content/early/2020/08/17/science.abd5223

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037