A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV

被引:1092
作者
Yuan, Meng [1 ]
Wu, Nicholas C. [1 ]
Zhu, Xueyong [1 ]
Lee, Chang-Chun D. [1 ]
So, Ray T. Y. [2 ]
Lv, Huibin [2 ]
Mok, Chris K. P. [2 ]
Wilson, Ian A. [1 ,3 ]
机构
[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA
[2] Univ Hong Kong, La Ka Shiny Fac Med, Sch Publ Hlth, HKU Pasteur Res Pole, Hong Kong, Peoples R China
[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
MONOCLONAL-ANTIBODY; SPIKE PROTEIN; CORONAVIRUS; NEUTRALIZATION;
D O I
10.1126/science.abb7269
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:630 / +
页数:27
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