Mary Wilson
Well-known member
Science 16 Mar 2021:
eabf2303
DOI: 10.1126/science.abf2303
Jun Zhang[SUP]1[/SUP],[SUP]2[/SUP],?, Yongfei Cai[SUP]1[/SUP],[SUP]2[/SUP],?, Tianshu Xiao[SUP]1[/SUP],[SUP]2[/SUP], Jianming Lu[SUP]3[/SUP], Hanqin Peng[SUP]1[/SUP], Sarah M. Sterling[SUP]4[/SUP],[SUP]5[/SUP], Richard M. Walsh Jr.[SUP]4[/SUP],[SUP]5[/SUP], Sophia Rits-Volloch[SUP]1[/SUP], Haisun Zhu[SUP]6[/SUP], Alec N. Woosley[SUP]6[/SUP], Wei Yang[SUP]6[/SUP], Piotr Sliz[SUP]1[/SUP],[SUP]2[/SUP],[SUP]5[/SUP], Bing Chen[SUP]1[/SUP],[SUP]2[/SUP],*
Abstract
Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing 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.
https://science.sciencemag.org/content/early/2021/03/16/science.abf2303
eabf2303
DOI: 10.1126/science.abf2303
Jun Zhang[SUP]1[/SUP],[SUP]2[/SUP],?, Yongfei Cai[SUP]1[/SUP],[SUP]2[/SUP],?, Tianshu Xiao[SUP]1[/SUP],[SUP]2[/SUP], Jianming Lu[SUP]3[/SUP], Hanqin Peng[SUP]1[/SUP], Sarah M. Sterling[SUP]4[/SUP],[SUP]5[/SUP], Richard M. Walsh Jr.[SUP]4[/SUP],[SUP]5[/SUP], Sophia Rits-Volloch[SUP]1[/SUP], Haisun Zhu[SUP]6[/SUP], Alec N. Woosley[SUP]6[/SUP], Wei Yang[SUP]6[/SUP], Piotr Sliz[SUP]1[/SUP],[SUP]2[/SUP],[SUP]5[/SUP], Bing Chen[SUP]1[/SUP],[SUP]2[/SUP],*
Abstract
Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing 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.
https://science.sciencemag.org/content/early/2021/03/16/science.abf2303