Evolution of the SARS-CoV-2 spike protein in the human host.
Evolution of the SARS-CoV-2 spike protein in the human host.
复制标题
DOI：
10.1038/s41467-022-28768-w
复制
发表时间：
2022-03-04
影响因子：
16.6
通讯作者：
Gamblin SJ
中科院分区：
文献类型：
--
作者：
Wrobel AG;Benton DJ;Roustan C;Borg A;Hussain S;Martin SR;Rosenthal PB;Skehel JJ;Gamblin SJ
最近出现的SARS-CoV-2变体在其表面刺突糖蛋白中含有与增加的传播和对中和抗体的抗性相关的多个取代。我们已经检查了B.1.1.7（α）和B.1.351（β）变体的刺突蛋白的结构和受体结合特性，以更好地了解病毒在人类中的进化。两种变体的刺突在受体结合结构域中具有相同的突变N501 Y。这种取代赋予更紧密的ACE 2结合，依赖于常见的早期取代，D 614 G。每一种变异刺突都获得了其他可能影响病毒发病机制的关键结构变化。来自α变体的刺突在结合ACE 2受体时比所研究的所有其他刺突更稳定。该特征与在S1-S2弗林蛋白酶位点获得更碱性的取代有关（也观察到关注的Delta、Kappa和Omicron变体），其允许接近完全切割。在β变体刺突中，新取代K417 N（也在Omicron变体中观察到）的存在与D 614 G组合，稳定了更开放的刺突三聚体，这是受体结合所需的构象。我们的观察表明，这些病毒已经进化到在人类中获得更大的传播能力。SARS-CoV-2的峰值一直在人群中发展。所关注的变体α和β进化以优化尖峰开放性，从而优化结合其受体ACE 2的能力、对受体的亲和力以及受体结合后的稳定性。
Recently emerged variants of SARS-CoV-2 contain in their surface spike glycoproteins multiple substitutions associated with increased transmission and resistance to neutralising antibodies. We have examined the structure and receptor binding properties of spike proteins from the B.1.1.7 (Alpha) and B.1.351 (Beta) variants to better understand the evolution of the virus in humans. Spikes of both variants have the same mutation, N501Y, in the receptor-binding domains. This substitution confers tighter ACE2 binding, dependent on the common earlier substitution, D614G. Each variant spike has acquired other key changes in structure that likely impact virus pathogenesis. The spike from the Alpha variant is more stable against disruption upon binding ACE2 receptor than all other spikes studied. This feature is linked to the acquisition of a more basic substitution at the S1-S2 furin site (also observed for the variants of concern Delta, Kappa, and Omicron) which allows for near-complete cleavage. In the Beta variant spike, the presence of a new substitution, K417N (also observed in the Omicron variant), in combination with the D614G, stabilises a more open spike trimer, a conformation required for receptor binding. Our observations suggest ways these viruses have evolved to achieve greater transmissibility in humans. The SARS-CoV-2 spike has been evolving in the human population. The variants of concern alpha and beta evolved to optimise spike openness and so ability to bind its receptor ACE2, the affinity towards the receptor, and stability upon receptor binding.
登录
查看更多内容
影响因子：
11.4
作者：
BOULAY, F;DOMS, RW;HELENIUS, A
通讯作者：
HELENIUS, A
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
64.8
作者：
Benton, Donald J.;Wrobel, Antoni G.;Gamblin, Steven J.
通讯作者：
Gamblin, Steven J.
DOI：
10.1073/pnas.2022586118
发表时间：
2021-03-02
影响因子：
11.1
作者：
Benton DJ;Wrobel AG;Roustan C;Borg A;Xu P;Martin SR;Rosenthal PB;Skehel JJ;Gamblin SJ
通讯作者：
Gamblin SJ