7Y3O

Crystal structure of SARS-CoV-2 receptor binding domain in complex with human antibody BIOLS56

7Y3O の概要

• エントリーDOI: 10.2210/pdb7y3o/pdb
• 分子名称: Heavy chain of BIOLS56, Light chain of BIOLS56, Spike protein S1, ... (5 entities in total)
• 機能のキーワード: sars-cov-2, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69492.45

構造登録者

Rao, X.,Gao, F.,Wu, Y.,Gao, F. (登録日: 2022-06-11, 公開日: 2023-12-27, 最終更新日: 2026-03-04)

主引用文献

Rao, X.,Zhao, R.,Tong, Z.,Guo, S.,Peng, W.,Liu, K.,Li, S.,Wu, L.,Tong, J.,Chai, Y.,Han, P.,Wang, F.,Jia, P.,Li, Z.,Zhao, X.,Li, D.,Zhang, R.,Zhang, X.,Zou, W.,Li, W.,Wang, Q.,Gao, G.F.,Wu, Y.,Dai, L.,Gao, F.
Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2.
Proc.Natl.Acad.Sci.USA, 120:e2314193120-e2314193120, 2023

PubMed Abstract: Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.

PubMed: 38109549
DOI: 10.1073/pnas.2314193120

実験手法

X-RAY DIFFRACTION (2.1 Å)