Structural impact on SARS-CoV-2 spike protein by D614G substitution

doi:10.1126/science.abf2303

GSTDTAP > 气候变化

DOI	10.1126/science.abf2303
	Structural impact on SARS-CoV-2 spike protein by D614G substitution
	Jun Zhang; Yongfei Cai; Tianshu Xiao; Jianming Lu; Hanqin Peng; Sarah M. Sterling; Richard M. Walsh; Sophia Rits-Volloch; Haisun Zhu; Alec N. Woosley; Wei Yang; Piotr Sliz; Bing Chen
	2021-04-30
发表期刊	Science
出版年	2021
英文摘要	Throughout the COVID-19 pandemic, epidemiologists have monitored the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with particular focus on the spike protein. An early variant with an aspartic acid (D) to glycine (G) mutation at position 614, D614G, rapidly became dominant and is maintained in current variants of concern. Zhang et al. investigated the structural basis for the increased spread of this variant, which does so even though it binds less tightly to the host receptor (see the Perspective by Choe and Farzan). Structural and biochemical studies on a full-length G614 spike trimer showed that there are interactions not present in D614 that prevent premature loss of the S1 subunit that binds angiotensin-converting enzyme 2. This stabilization effectively increases the number of spikes that can facilitate infection. Science , this issue p. [525][1]; see also p. [466][2] 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. [1]: /lookup/doi/10.1126/science.abf2303 [2]: /lookup/doi/10.1126/science.abi4711
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/325043
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jun Zhang,Yongfei Cai,Tianshu Xiao,et al. Structural impact on SARS-CoV-2 spike protein by D614G substitution[J]. Science,2021.
APA	Jun Zhang.,Yongfei Cai.,Tianshu Xiao.,Jianming Lu.,Hanqin Peng.,...&Bing Chen.(2021).Structural impact on SARS-CoV-2 spike protein by D614G substitution.Science.
MLA	Jun Zhang,et al."Structural impact on SARS-CoV-2 spike protein by D614G substitution".Science (2021).