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 Cited by 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: 40627497DOI: 10.1016/j.celrep.2025.115948 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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