8SIR

Crystal structure of SARS-CoV-2 spike receptor-binding domain in complex with broadly neutralizing antibody CC25.54 Fab

8SIR の概要

• エントリーDOI: 10.2210/pdb8sir/pdb
• 分子名称: Spike protein S1, CC25.54 Fab heavy chain, CC25.54 Fab light chain, ... (4 entities in total)
• 機能のキーワード: bnab, sars-cov-2, broadly neutralizing antibody, spike, rbd, immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 72703.98

構造登録者

Liu, H.,Wilson, I.A. (登録日: 2023-04-16, 公開日: 2024-03-13, 最終更新日: 2025-07-30)

主引用文献

Song, G.,Yuan, M.,Liu, H.,Capozzola, T.,Lin, R.N.,Torres, J.L.,He, W.T.,Musharrafieh, R.,Dueker, K.,Zhou, P.,Callaghan, S.,Mishra, N.,Yong, P.,Anzanello, F.,Avillion, G.,Vo, A.L.,Li, X.,Zhang, Y.,Makhdoomi, M.,Feng, Z.,Zhu, X.,Peng, L.,Nemazee, D.,Safonova, Y.,Briney, B.,Ward, A.B.,Burton, D.R.,Wilson, I.A.,Andrabi, R.
Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.
Cell Rep, 44:115948-115948, 2025

PubMed Abstract: Developing broad coronavirus vaccines hinges on identifying and understanding the molecular basis of conserved spike epitopes targeted by broadly neutralizing antibodies (bnAbs). Building on our earlier work identifying sarbecovirus receptor-binding domain (RBD) group 1 and 2 bnAbs, we now show that several of these antibodies retain neutralizing activity against highly mutated SARS-CoV-2 variants, including BA.2.86 and JN.1. Structural studies reveal that group 1 bnAbs use recurrent germline-encoded heavy-chain complementarity-determining region 3 (CDRH3) features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-defined "site V" on the RBD and destabilize spike trimer. Notably, site V remains largely unchanged across SARS-CoV-2 variants and is conserved among diverse sarbecoviruses, highlighting its potential as a broad vaccine target. Our findings underscore the need for targeted vaccine strategies to induce immunofocused B cell responses to escape resistant subdominant spike RBD bnAb epitopes.

PubMed: 40627497
DOI: 10.1016/j.celrep.2025.115948

実験手法

X-RAY DIFFRACTION (3.3 Å)