7TAT
SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody Fab fragment (two receptor-binding domains open)
Summary for 7TAT
| Entry DOI | 10.2210/pdb7tat/pdb |
| EMDB information | 25784 |
| Descriptor | Spike glycoprotein, S2K146 Fab heavy chain, S2K146 Fab light chain, ... (5 entities in total) |
| Functional Keywords | sars-cov-2, covid-19, spike glycoprotein, fusion protein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein-immune system complex, viral protein/immune system |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 512834.02 |
| Authors | Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2021-12-21, release date: 2022-01-12, Last modification date: 2022-02-09) |
| Primary citation | Park, Y.J.,De Marco, A.,Starr, T.N.,Liu, Z.,Pinto, D.,Walls, A.C.,Zatta, F.,Zepeda, S.K.,Bowen, J.E.,Sprouse, K.R.,Joshi, A.,Giurdanella, M.,Guarino, B.,Noack, J.,Abdelnabi, R.,Foo, S.C.,Rosen, L.E.,Lempp, F.A.,Benigni, F.,Snell, G.,Neyts, J.,Whelan, S.P.J.,Virgin, H.W.,Bloom, J.D.,Corti, D.,Pizzuto, M.S.,Veesler, D. Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry. Science, 375:449-454, 2022 Cited by PubMed Abstract: Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity. PubMed: 34990214DOI: 10.1126/science.abm8143 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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