PDF(Pubmed)
Abstract：
Spike (S) glycoprotein of SARS-CoV2 exists chiefly in two conformations, open and closed. Most previous structural studies on S protein have been conducted at pH 8.0, but knowledge of the conformational propensities under both physiological and endosomal pH conditions is important to inform vaccine development. Our current study employed single-particle cryoelectron microscopy to visualize multiple states of open and closed conformations of S protein at physiological pH 7.4 and near-physiological pH 6.5 and pH 8.0. Propensities of open and closed conformations were found to differ with pH changes, whereby around 68% of S protein exists in open conformation at pH 7.4. Furthermore, we noticed a continuous movement in the N-terminal domain, receptor-binding domain (RBD), S2 domain, and stalk domain of S protein conformations at various pH values. Several key residues involving RBD-neutralizing epitopes are differentially exposed in each conformation. This study will assist in developing novel therapeutic measures against SARS-CoV2.
摘要：
SARS-CoV2的Spike（S）糖蛋白主要存在两种构象，打开和关闭。以前对S蛋白的大多数结构研究都是在pH8.0下进行的，但是在生理和内体pH条件下的构象倾向的知识对于疫苗开发很重要。我们目前的研究采用单粒子低温电子显微镜观察S蛋白在生理pH7.4和接近生理pH6.5和pH8.0时的开放和封闭构象的多种状态。发现开放和封闭构象的倾向随pH变化而不同，其中约68％的S蛋白在pH7.4下以开放构象存在。此外，我们注意到N端域的连续运动，受体结合域（RBD），S2域,和在各种pH值下S蛋白构象的茎结构域。涉及RBD中和表位的几个关键残基在每种构象中差异暴露。这项研究将有助于开发针对SARS-CoV2的新型治疗措施。
