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完整病毒颗粒上的SARS-CoV-2突刺蛋白结构获解析
2020-08-19 17:14

英国剑桥大学John A. G. Briggs课题组解析出完整病毒颗粒上SARS-CoV-2突刺蛋白的结构与分布。相关论文于2020年8月17日在线发表在《自然》杂志上。

研究人员表示,严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)病毒颗粒被脂质双层包围,并从中伸出突刺(S)蛋白三聚体。高度糖基化的S三聚体结合ACE2受体并介导病毒粒子进入靶细胞。S表现出广泛的构象灵活性:它调节其受体结合位点的暴露,并随后进行完整的结构重排,从而驱动病毒膜和细胞膜融合。可溶的、过表达的、纯化的S蛋白结构和构象已通过冷冻电子显微镜技术进行了详细研究。然而,还没有表征S在病毒体表面上的结构和分布。
 
研究人员了冷冻电镜和层析成像技术对完整的SARS-CoV-2病毒体进行了成像,从而确定了病毒体表面上的S结构的高分辨率结构、构象柔韧性和三聚体分布。这些结果揭示了存在于病毒体上的S的构象,并为了解在感染或疫苗接种过程中S与中和抗体之间的相互作用提供了基础。
 
附:英文原文

Title: Structures and distributions of SARS-CoV-2 spike proteins on intact virions

Author: Zunlong Ke, Joaquin Oton, Kun Qu, Mirko Cortese, Vojtech Zila, Lesley McKeane, Takanori Nakane, Jasenko Zivanov, Christopher J. Neufeldt, Berati Cerikan, John M. Lu, Julia Peukes, Xiaoli Xiong, Hans-Georg Krusslich, Sjors H. W. Scheres, Ralf Bartenschlager, John A. G. Briggs

Issue&Volume: 2020-08-17

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude1. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells2–6. S exhibits extensive conformational flexibility: it modulates exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes2,7,8. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy2,7,9–12. The structure and distribution of S on the virion surface, however, has not been characterized. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S present on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.

DOI: 10.1038/s41586-020-2665-2

Source: https://www.nature.com/articles/s41586-020-2665-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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