Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo-electron microscopy.

Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo-electron microscopy.
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DOI:
10.1002/pro.3048
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发表时间:
2017-01
期刊:
影响因子:
8
通讯作者:
Veesler, David
Veesler, David
中科院分区:
生物学3区
文献类型:
--
作者:
Walls, Alexandra;Tortorici, M. Alejandra;Bosch, Berend-Jan;Frenz, Brandon;Rottier, Peter J. M.;DiMaio, Frank;Rey, Felix A.;Veesler, David

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在过去15年中,两次全球爆发致命肺炎证明了冠状病毒的巨大流行潜力。冠状病毒进入细胞是由跨膜刺激性糖蛋白S介导的,它形成一个三聚体,携带受体结合和膜融合功能。尽管冠状病毒S糖蛋白具有生物医学上的重要性,但事实证明,它们很难作为结构表征的靶点,从而排除了对具有生物相关性的三聚体的高分辨率研究。单粒子冷冻电子显微镜技术的最新发展使我们能够确定冠状病毒S糖蛋白三聚体的第一结构,这为理解病毒入侵的机制提供了一个框架,并提出了对该病毒家族的潜在抑制策略。在这里,我们描述了促成这一突破的关键因素。
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.
电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
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