Overduin Michael, Kervin Troy A, Tran Anh
Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
iScience. 2022 Aug 19;25(8):104722. doi: 10.1016/j.isci.2022.104722. Epub 2022 Jul 4.
Membrane recognition by viral spike proteins is critical for infection. Here we show the host cell membrane-binding surfaces of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike variants Alpha, Beta, Gamma, Delta, Epsilon, Kappa, and Omicron as well as SARS-CoV-1 and pangolin and bat relatives. They show increases in membrane binding propensities over time, with all spike head mutations in variants, and particularly BA.1, impacting the protein's affinity to cell membranes. Comparison of hundreds of structures yields a progressive model of membrane docking in which spike protein trimers shift from initial perpendicular stances to increasingly tilted positions that draw viral particles alongside host cell membranes before optionally engaging angiotensin-converting enzyme 2 (ACE2) receptors. This culminates in the assembly of the symmetric fusion apparatus, with enhanced membrane interactions of variants explaining their unique cell fusion capacities and COVID-19 disease transmission rates.
病毒刺突蛋白对膜的识别对于感染至关重要。在此，我们展示了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突变体Alpha、Beta、Gamma、Delta、Epsilon、Kappa和Omicron以及SARS-CoV-1以及穿山甲和蝙蝠相关病毒的宿主细胞膜结合表面。随着时间的推移，它们的膜结合倾向增加，变体中的所有刺突头部突变，尤其是BA.1，都会影响蛋白质对细胞膜的亲和力。对数百个结构的比较产生了一个膜对接的渐进模型，其中刺突蛋白三聚体从最初的垂直姿态转变为越来越倾斜的位置，在选择性地与血管紧张素转换酶2（ACE2）受体结合之前，将病毒颗粒拉到宿主细胞膜旁边。这最终导致对称融合装置的组装，变体增强的膜相互作用解释了它们独特的细胞融合能力和COVID-19疾病传播率。
