Zhang Jun, Cai Yongfei, Xiao Tianshu, Lu Jianming, Peng Hanqin, Sterling Sarah M, Walsh Richard M, Rits-Volloch Sophia, Sliz Piotr, Chen Bing
bioRxiv. 2020 Oct 20:2020.10.13.337980. doi: 10.1101/2020.10.13.337980.
Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing pandemic, appears to facilitate rapid viral spread. The G614 variant has now replaced the D614-carrying virus as the dominant circulating strain. We report here cryo-EM structures of a full-length S trimer carrying G614, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain (RBD). A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity. The loop transition may also modulate structural rearrangements of S protein required for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.
在导致当前大流行的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突（S）蛋白中，第614位的天冬氨酸被甘氨酸取代，这似乎有助于病毒快速传播。G614变体现已取代携带D614的病毒，成为主要的流行毒株。我们在此报告携带G614的全长S三聚体的冷冻电镜结构，其采用三种不同的预融合构象，主要区别在于一个受体结合域（RBD）的位置。在D614 S三聚体中无序的一个环在G614刺突的一个原体中的结构域之间楔入。这种额外的相互作用似乎可防止G614三聚体过早解离，有效增加功能性刺突的数量并增强感染性。环的转变也可能调节膜融合所需的S蛋白的结构重排。这些发现扩展了我们对病毒进入的理解，并为疫苗开发提供了一种改进的免疫原。
