7D00

S protein of SARS-CoV-2 in complex bound with FabP5A-1B8

7D00 の概要

• エントリーDOI: 10.2210/pdb7d00/pdb
• EMDBエントリー: 30523
• 分子名称: Spike glycoprotein, IG c642_heavy_IGHV3-53_IGHD1-26_IGHJ6,chain H of FabP5A-1B8,IGH@ protein, IGL c4203_light_IGKV1-9_IGKJ4,Uncharacterized protein, ... (5 entities in total)
• 機能のキーワード: sars-cov-2, antibody, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 586290.96

構造登録者

Yan, R.H.,Zhang, Y.Y.,Li, Y.N.,Zhou, Q. (登録日: 2020-09-09, 公開日: 2021-03-10, 最終更新日: 2021-05-19)

主引用文献

Yan, R.,Wang, R.,Ju, B.,Yu, J.,Zhang, Y.,Liu, N.,Wang, J.,Zhang, Q.,Chen, P.,Zhou, B.,Li, Y.,Shen, Y.,Zhang, S.,Tian, L.,Guo, Y.,Xia, L.,Zhong, X.,Cheng, L.,Ge, X.,Zhao, J.,Wang, H.W.,Wang, X.,Zhang, Z.,Zhang, L.,Zhou, Q.
Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.
Cell Res., 31:517-525, 2021

PubMed Abstract: Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.

PubMed: 33731853
DOI: 10.1038/s41422-021-00487-9

実験手法

ELECTRON MICROSCOPY (3 Å)