The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2.
The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2.
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DOI：
10.1073/pnas.2022586118
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发表时间：
2021-03-02
影响因子：
11.1
通讯作者：
Gamblin SJ
中科院分区：
文献类型：
--
作者：
Benton DJ;Wrobel AG;Roustan C;Borg A;Xu P;Martin SR;Rosenthal PB;Skehel JJ;Gamblin SJ
与初始分离株的刺突蛋白相比，大多数当前严重急性呼吸综合征冠状病毒2型分离株的刺突蛋白含有D 614 G置换。在这项研究中，我们提出了高分辨率，单粒子冷冻电子显微镜结构的G614穗变种，表明它采用了主要开放的构象，不像D 614穗，主要是封闭的。我们的结论是D 614 G取代促进“开放”的穗，引发它的受体ACE 2的结合，并可能在膜融合的后续作用。观察到的G614刺突的开放构象可能是目前病毒报告的感染性增加及其目前优势的原因。目前流行的大多数严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有突变的刺突糖蛋白，其包含D 614 G取代。几项研究表明，这种取代的尖峰与更高的病毒感染性有关。我们使用冷冻电子显微镜比较G614和D 614尖峰，并显示G614突变尖峰采用了一系列更开放的构象，可能有助于结合到SARS-CoV-2受体，ACE 2，以及随后的病毒膜融合所需的结构重排。
The spike proteins of most current severe acute respiratory syndrome coronavirus 2 isolates contain a D614G substitution, by comparison with the spike protein of initial isolates. In this study we present high-resolution, single-particle cryo-electron microscopy structures of the G614 spike variant showing that it adopts a predominantly open conformation, unlike the D614 spike that is mostly closed. We conclude that the D614G substitution promotes “opening” of the spike, priming it for binding to the receptor ACE2 and possibly for its subsequent role in membrane fusion. The observed open conformation of the G614 spike may be the reason for the current virus’ reported increased infectivity and its current predominance. The majority of currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses have mutant spike glycoproteins that contain the D614G substitution. Several studies have suggested that spikes with this substitution are associated with higher virus infectivity. We use cryo-electron microscopy to compare G614 and D614 spikes and show that the G614 mutant spike adopts a range of more open conformations that may facilitate binding to the SARS-CoV-2 receptor, ACE2, and the subsequent structural rearrangements required for viral membrane fusion.
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DOI：
10.1126/science.abd3255
发表时间：
2020-11-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Toelzer C;Gupta K;Yadav SKN;Borucu U;Davidson AD;Kavanagh Williamson M;Shoemark DK;Garzoni F;Staufer O;Milligan R;Capin J;Mulholland AJ;Spatz J;Fitzgerald D;Berger I;Schaffitzel C
通讯作者：
Schaffitzel C
影响因子：
64.8
作者：
Ke, Zunlong;Oton, Joaquin;Briggs, John A. G.
通讯作者：
Briggs, John A. G.
影响因子：
30.3
作者：
Weissman D;Alameh MG;de Silva T;Collini P;Hornsby H;Brown R;LaBranche CC;Edwards RJ;Sutherland L;Santra S;Mansouri K;Gobeil S;McDanal C;Pardi N;Hengartner N;Lin PJC;Tam Y;Shaw PA;Lewis MG;Boesler C;Şahin U;Acharya P;Haynes BF;Korber B;Montefiori DC
通讯作者：
Montefiori DC
影响因子：
48
作者：
Zheng SQ;Palovcak E;Armache JP;Verba KA;Cheng Y;Agard DA
通讯作者：
Agard DA
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.