8SIR

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

Summary for 8SIR

• Entry DOI: 10.2210/pdb8sir/pdb
• Descriptor: Spike protein S1, CC25.54 Fab heavy chain, CC25.54 Fab light chain, ... (4 entities in total)
• Functional Keywords: bnab, sars-cov-2, broadly neutralizing antibody, spike, rbd, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 72703.98

Authors

Liu, H.,Wilson, I.A. (deposition date: 2023-04-16, release date: 2024-03-13, Last modification date: 2025-07-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.3 Å)