Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
复制标题
与 ACE2 受体结合的 SARS-CoV-2 刺突受体结合域的结构
DOI：
10.1038/s41586-020-2180-5
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发表时间：
2020-03-30
期刊：
影响因子：
64.8
通讯作者：
Wang, Xinquan
中科院分区：
文献类型：
--
作者：
Lan, Jun;Ge, Jiwan;Wang, Xinquan
一种新型高致病性冠状病毒（严重急性呼吸综合征冠状病毒-2，SARS-CoV-2）从2019年12月开始在中国湖北省武汉市爆发，迅速蔓延到全国和世界其他国家。在这里，为了更好地理解在原子水平上感染的初始步骤，我们确定了与细胞受体ACE 2结合的SARS-CoV-2刺突蛋白的受体结合域（RBD）的晶体结构。SARS-CoV-2 RBD的总体ACE 2结合模式与SARS-CoV RBD几乎相同，后者也使用ACE 2作为细胞受体。结构分析鉴定了SARS-CoV-2 RBD中对ACE 2结合至关重要的残基，其中大多数是高度保守的或与SARS-CoV RBD中的残基具有相似的侧链性质。这种结构和序列上的相似性强烈表明SARS-CoV-2和SARS-CoV RBD之间的趋同进化，以改善与ACE 2的结合，尽管SARS-CoV-2并不聚集在SARS和SARS相关的冠状病毒内。还分析了靶向RBD的两种SARS-CoV抗体的表位与SARS-CoV-2 RBD的结合，为未来鉴定交叉反应性抗体提供了见解。
A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world, –. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses, –,. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.