8VPF
Structure of SARS-CoV spike in complex with CoV1-65 Fab (NTD-bound)
Summary for 8VPF
| Entry DOI | 10.2210/pdb8vpf/pdb |
| EMDB information | 43407 |
| Descriptor | Spike glycoprotein, CoV1-65 antibody heavy chain, CoV1-65 antibody light chain, ... (6 entities in total) |
| Functional Keywords | sars-cov, spike, monoclonal antibody, complex, ntd, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus More |
| Total number of polymer chains | 9 |
| Total formula weight | 566796.55 |
| Authors | Bangaru, S.,Ward, A.B. (deposition date: 2024-01-16, release date: 2025-03-19, Last modification date: 2025-06-04) |
| Primary citation | Suryadevara, N.,Kose, N.,Bangaru, S.,Binshtein, E.,Munt, J.,Martinez, D.R.,Schafer, A.,Myers, L.,Scobey, T.D.,Carnahan, R.H.,Ward, A.B.,Baric, R.S.,Crowe Jr., J.E. Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV. J.Clin.Invest., 135:-, 2024 Cited by PubMed Abstract: The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target the SARS-CoV-2 NTD potently neutralize the virus. This finding suggests the NTD may contribute, in part, to protective immunity. Pansarbecovirus antibodies are desirable for broad protection, but the NTD region of SARS-CoV and SARS-CoV-2 exhibit a high level of sequence divergence; therefore, cross-reactive NTD-specific antibodies are unexpected, and there is no structure of a SARS-CoV NTD-specific antibody in complex with NTD. Here, we report a monoclonal antibody COV1-65, encoded by the IGHV1-69 gene, that recognizes the NTD of SARS-CoV S protein. A prophylaxis study showed the mAb COV1-65 prevented disease when administered before SARS-CoV challenge of BALB/c mice, an effect that requires intact fragment crystallizable region (Fc) effector functions for optimal protection in vivo. The footprint on the S protein of COV1-65 is near to functional components of the S2 fusion machinery, and the selection of COV1-65 escape mutant viruses identified critical residues Y886H and Q974H, which likely affect the epitope through allosteric effects. Structural features of the mAb COV1-65-SARS-CoV antigen interaction suggest critical antigenic determinants that should be considered in the rational design of sarbecovirus vaccine candidates. PubMed: 39589795DOI: 10.1172/JCI178880 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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