7UKL
Cryo-EM structure of Antibody 12-16 in complex with prefusion SARS-CoV-2 Spike glycoprotein
Summary for 7UKL
| Entry DOI | 10.2210/pdb7ukl/pdb |
| EMDB information | 26583 26584 |
| Descriptor | 12-16 Fab Light Chain, Spike glycoprotein, 12-16 Fab Heavy Chain, ... (4 entities in total) |
| Functional Keywords | neutralizing antibody, viral fusion protein, sars-cov-2, viral protein-immune system complex, viral protein/immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 9 |
| Total formula weight | 513055.49 |
| Authors | Casner, R.G.,Shapiro, L. (deposition date: 2022-04-01, release date: 2023-10-04, Last modification date: 2024-10-30) |
| Primary citation | Liu, L.,Casner, R.G.,Guo, Y.,Wang, Q.,Iketani, S.,Chan, J.F.,Yu, J.,Dadonaite, B.,Nair, M.S.,Mohri, H.,Reddem, E.R.,Yuan, S.,Poon, V.K.,Chan, C.C.,Yuen, K.Y.,Sheng, Z.,Huang, Y.,Bloom, J.D.,Shapiro, L.,Ho, D.D. Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking. Immunity, 56:2442-, 2023 Cited by PubMed Abstract: SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.1 intranasally. Structurally, both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, uncovering a site of vulnerability on SARS-CoV-2 spike. These antibodies prevented viral receptor engagement by locking the receptor-binding domain (RBD) of spike in the down conformation, revealing a mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but such mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines. PubMed: 37776849DOI: 10.1016/j.immuni.2023.09.003 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.09 Å) |
Structure validation
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