Walls Alexandra, Tortorici M Alejandra, Bosch Berend-Jan, Frenz Brandon, Rottier Peter J M, DiMaio Frank, Rey Felix A, Veesler David
Department of Biochemistry, University of Washington, Seattle, Washington, 98195.
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.
Protein Sci. 2017 Jan;26(1):113-121. doi: 10.1002/pro.3048. Epub 2016 Oct 18.
The tremendous pandemic potential of coronaviruses was demonstrated twice in the last 15 years by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. Despite their biomedical importance, coronavirus S glycoproteins have proven difficult targets for structural characterization, precluding high-resolution studies of the biologically relevant trimer. Recent technological developments in single particle cryo-electron microscopy allowed us to determine the first structure of a coronavirus S glycoprotein trimer which provided a framework to understand the mechanisms of viral entry and suggested potential inhibition strategies for this family of viruses. Here, we describe the key factors that enabled this breakthrough.
在过去15年里，冠状病毒两次引发全球致命肺炎大流行，充分显示出其巨大的疫情潜力。冠状病毒进入细胞是由跨膜刺突糖蛋白S介导的，该蛋白形成一个三聚体，兼具受体结合和膜融合功能。尽管冠状病毒S糖蛋白具有重要的生物医学意义，但事实证明，对其进行结构表征具有挑战性，阻碍了对生物学上相关三聚体的高分辨率研究。单颗粒冷冻电子显微镜技术最近的发展使我们能够确定冠状病毒S糖蛋白三聚体的首个结构，这为理解病毒进入机制提供了框架，并为该病毒家族提出了潜在的抑制策略。在此，我们描述促成这一突破的关键因素。
