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.

中文翻译：

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D614G 替代对 SARS-CoV-2 刺突蛋白的结构影响

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的刺突 (S) 蛋白 614 位上的甘氨酸取代天冬氨酸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。我们在这里报告了携带 G614 的全长 S 三聚体的冷冻电镜结构，它采用三种不同的融合前构象，主要区别在于一个受体结合域 (RBD) 的位置。D614 S 三聚体中无序的环楔入 G614 尖峰中原聚体内的域之间。这种增加的相互作用似乎可以防止 G614 三聚体过早解离，有效地增加功能性尖峰的数量并增强感染性。环转换还可以调节膜融合所需的 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，并提出了一种用于疫苗开发的改进免疫原。