Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Nature. 2020 Dec;588(7838):498-502. doi: 10.1038/s41586-020-2665-2. Epub 2020 Aug 17.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells. 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. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy, 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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）病毒粒子被一个脂质双层所包围，其表面突出有刺突（S）蛋白三聚体。高度糖基化的 S 三聚体与血管紧张素转换酶 2 受体结合，并介导病毒粒子进入靶细胞。S 表现出广泛的构象灵活性：它调节受体结合部位的暴露，随后经历完全的结构重排，驱动病毒和细胞膜的融合。使用低温电子显微镜详细研究了可溶性、过表达、纯化的 S 蛋白的结构和构象，但病毒粒子表面上 S 的结构和分布仍然未知。在这里，我们应用低温电子显微镜和断层扫描技术来对完整的 SARS-CoV-2 病毒粒子进行成像，并确定病毒粒子表面上 S 三聚体的高分辨率结构、构象灵活性和分布。这些结果揭示了病毒粒子上 S 的构象，并为理解感染或接种疫苗过程中 S 与中和抗体之间的相互作用提供了基础。
