SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
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DOI：
10.1038/s41594-020-0468-7
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发表时间：
2020-08
影响因子：
16.8
通讯作者：
Gamblin SJ
中科院分区：
文献类型：
--
作者：
Wrobel AG;Benton DJ;Xu P;Roustan C;Martin SR;Rosenthal PB;Skehel JJ;Gamblin SJ
SARS-CoV-2被认为是从蝙蝠中出现的，可能是通过第二宿主。在这里，我们研究了SARS-CoV-2的刺突（S）糖蛋白与密切相关的蝙蝠病毒RaTG 13的关系。我们确定了S蛋白和SARS-CoV-2在弗林蛋白酶切割和未切割形式下的cryo-EM结构;并将其与最近报道的未切割SARS-CoV-2 S的结构进行了比较。我们还从生物化学上表征了它们对SARS-CoV-2受体ACE 2的相对稳定性和亲和力。虽然人类和蝙蝠病毒S蛋白的总体结构相似，但它们的特性存在关键差异，包括更稳定的人类S蛋白的预切割形式以及SARS-CoV-2与人类受体的结合紧密约1000倍。这些观察结果表明，在弗林蛋白酶切割位点的切割降低了SARS-CoV-2 S的整体稳定性，并促进了S与ACE 2受体结合所需的开放构象的采用。
SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with that of a closely related bat virus, RaTG13. We determined cryo-EM structures for both S proteins, and for SARS-CoV-2, in furin-cleaved and uncleaved forms; and compared them to recently reported structures for uncleaved SARS-CoV-2 S. We have also characterised biochemically their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable pre-cleavage form of human S and about 1000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
48
作者：
Kastner, Berthold;Fischer, Niels;Stark, Holger
通讯作者：
Stark, Holger
影响因子：
3.2
作者：
Chan, Che-Man;Woo, Patrick C. Y.;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
DOI：
10.1073/pnas.1407087111
发表时间：
2014-10-21
影响因子：
11.1
作者：
Millet, Jean Kaoru;Whittaker, Gary R.
通讯作者：
Whittaker, Gary R.
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.