Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Science. 2021 Apr 30;372(6541):525-530. doi: 10.1126/science.abf2303. Epub 2021 Mar 16.
Substitution for aspartic acid (D) by glycine (G) at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. Here, we report cryo-electron microscopy structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations that differ primarily by the position of one receptor-binding domain. 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-and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.
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 位天冬氨酸（D）被甘氨酸（G）取代似乎促进了病毒的快速传播。G614 株及其最近的变体现在是主要的循环形式。在这里，我们报告了全长 G614 S 三聚体的冷冻电镜结构，该三聚体采用三种不同的预融合构象，主要区别在于一个受体结合结构域的位置。D614 S 三聚体中无序的环在 G614 刺突的一个原体内的结构域之间楔入。这种额外的相互作用似乎阻止了 G614 三聚体的过早解离，有效地增加了功能刺突的数量并提高了感染力，并调节了膜融合的结构重排。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。
