The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins, which are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S protein from SARS-CoV-2 variants has revealed this structural adaptation at high resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures, and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Taken together, our data are consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of the S protein.

中文翻译：

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不同 SARS-CoV-2 变体的病毒粒子形态和病毒刺突蛋白结构。


SARS-CoV-2 变体的进化伴随着适应性增加的刺突 （S） 蛋白的结构变化，刺突 （S） 蛋白是适应性免疫反应的主要靶标。对 SARS-CoV-2 变体的可溶性 S 蛋白进行单颗粒冷冻电镜分析，在高分辨率下揭示了这种结构适应。对完整病毒粒子的 S 三聚体原位分析有可能为 S 结构和病毒粒子形态提供更具有功能相关性的见解。在这里，我们通过冷冻电子显微镜和断层扫描表征了 B.1、Alpha、Beta、Gamma、Delta、Kappa 和 Mu 变体，评估了 S 切割、病毒粒子形态、S 掺入、“原位”高分辨率 S 结构和 S 构象状态的范围。我们没有发现病毒粒子形态适应性变化的证据，但描述了 S 蛋白中的多个不同位置，其中氨基酸变化改变了局部蛋白质结构。综上所述，我们的数据与一个模型一致，在该模型中，从刺突顶部到底部的多个位置的氨基酸变化会导致结构变化，从而调节 S 蛋白的构象动力学。