Functional importance of the D614G mutation in the SARS-CoV-2 spike protein.

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein.
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DOI:
10.1016/j.bbrc.2020.11.026
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发表时间:
2021-01-29
影响因子:
3.1
通讯作者:
Choe H
Choe H
中科院分区:
生物学4区
文献类型:
--
作者:
Jackson CB;Zhang L;Farzan M;Choe H

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严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是一种有包膜的病毒,它与细胞受体血管紧张素转换酶2(ACE 2)结合,通过病毒粒子表面的S糖蛋白进入宿主细胞。与SARS-CoV-2的参考株相比,目前流行的大多数分离株具有S蛋白变体,其特征在于氨基酸位置614(D 614 G)处的天冬氨酸至甘氨酸取代。残基614位于受体结合结构域(RBD)之外,并且突变不改变单体S蛋白对ACE 2的亲和力。然而,与S(D 614)相比,S(G614)通过S-假型载体介导更有效的ACE 2介导的细胞转导,并且通过活SARS-CoV-2更有效地感染细胞和动物。本文总结并综合了D 614 G尖峰突变的流行病学和功能观察,重点关注该突变的生化和细胞生物学影响及其对S蛋白功能的后果。我们进一步讨论了这些最新发现在当前全球大流行背景下的意义。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. Compared to the reference strain of SARS-CoV-2, the majority of currently circulating isolates possess an S protein variant characterized by an aspartic acid-to-glycine substitution at amino acid position 614 (D614G). Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2. This review summarizes and synthesizes the epidemiological and functional observations of the D614G spike mutation, with focus on the biochemical and cell-biological impact of this mutation and its consequences for S protein function. We further discuss the significance of these recent findings in the context of the current global pandemic.
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