Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Science. 2020 May 8;368(6491):630-633. doi: 10.1126/science.abb7269. Epub 2020 Apr 3.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the "up" conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 疫情现已成为全球性大流行，但目前对该病毒的抗原性知之甚少。因此，我们测定了先前从 SARS 康复患者中分离出的中和抗体 CR3022 与 SARS-CoV-2 刺突 (S) 蛋白受体结合域 (RBD) 复合物的晶体结构，分辨率为 3.1埃。CR3022 靶向一个高度保守的表位，位于受体结合位点之外，使 SARS-CoV-2 和 SARS-CoV 之间能够发生交叉反应性结合。结构建模进一步表明，只有当三聚体 S 蛋白上的至少两个 RBD 处于“向上”构象并略微旋转时，CR3022 才能结合到结合表位。这些结果为抗体识别 SARS-CoV-2 提供了分子见解。
