7FCQ

Crystallographic structure of neutralizing antibody P14-44 in complex with SARS-CoV-2 spike receptor-binding Domain (RBD)

7FCQ の概要

• エントリーDOI: 10.2210/pdb7fcq/pdb
• 分子名称: Spike protein S1, P14-44 antibody Fab fragment heavy chain, P14-44 antibody Fab fragment light chain, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, rbd, neutralizing antibodies, antiviral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71551.57

構造登録者

Zheng, P.,Jin, T. (登録日: 2021-07-15, 公開日: 2022-06-15, 最終更新日: 2024-11-13)

主引用文献

Zou, J.,Li, L.,Zheng, P.,Liang, W.,Hu, S.,Zhou, S.,Wang, Y.,Zhao, J.,Yuan, D.,Liu, L.,Wu, D.,Xu, M.,Zhang, F.,Zhu, M.,Wu, Z.,Cao, X.,Ni, M.,Ling, X.,Wu, Y.,Kuang, Z.,Hu, M.,Li, J.,Li, X.,Guo, X.,Xu, T.,Jiang, H.,Gao, C.,Yu, M.,Liu, J.,Zhong, N.,Zhou, J.,Huang, J.A.,Jin, T.,He, J.
Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.
J.Clin.Invest., 132:-, 2022

PubMed Abstract: Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.

PubMed: 35108220
DOI: 10.1172/JCI154987

実験手法

X-RAY DIFFRACTION (1.89 Å)