Structures and distributions of SARS-CoV-2 spike proteins on intact virions
Structures and distributions of SARS-CoV-2 spike proteins on intact virions
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DOI：
10.1038/s41586-020-2665-2
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发表时间：
2020-08-17
期刊：
影响因子：
64.8
通讯作者：
Briggs, John A. G.
中科院分区：
文献类型：
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作者：
Ke, Zunlong;Oton, Joaquin;Briggs, John A. G.
严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）病毒粒子被脂质双层包围，刺突（S）蛋白三聚体从脂质双层突出（1）。高度糖基化的S三聚体与血管紧张素转化酶2受体结合，并介导病毒体进入靶细胞（2-6）。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，随后经历完全的结构重排，以驱动病毒和细胞膜的融合（2，7，8）。可溶的、过表达的、纯化的S蛋白的结构和构象已经使用冷冻电子显微镜进行了详细研究（2，7，9 -12），但是S在病毒体表面的结构和分布仍然未知。在这里，我们应用冷冻电子显微镜和断层扫描成像完整的SARS-CoV-2病毒粒子，并确定高分辨率的结构，构象的灵活性和分布的S三聚体在病毒粒子表面原位。这些结果揭示了S在病毒粒子上的构象，并为理解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。完整的SARS冠状病毒2型纤突蛋白三聚体的构象和分布（SARS-CoV-2）病毒粒子的相互作用，并为理解刺突蛋白与中和抗体的相互作用提供了基础。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude(1). Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells(2-6). S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes(2,7,8). The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy(2,7,9-12), but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.Cryo-electron microscopy and tomography studies reveal the structures, conformations and distributions of spike protein trimers on intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions and provide a basis for understanding the interactions of the spike protein with neutralizing antibodies.