7AKJ
Structure of the SARS-CoV spike glycoprotein in complex with the 47D11 neutralizing antibody Fab fragment
Summary for 7AKJ
Entry DOI | 10.2210/pdb7akj/pdb |
EMDB information | 11813 |
Descriptor | Spike glycoprotein, 47D11 neutralizing antibody heavy chain, 47D11 neutralizing antibody light chain, ... (7 entities in total) |
Functional Keywords | sars-cov, spike, neutralizing antibody, viral protein |
Biological source | SARS coronavirus WH20 More |
Total number of polymer chains | 9 |
Total formula weight | 489975.40 |
Authors | Fedry, J.,Hurdiss, D.L.,Wang, C.,Li, W.,Obal, G.,Drulyte, I.,Howes, S.C.,van Kuppeveld, F.J.M.,Foerster, F.,Bosch, B.J. (deposition date: 2020-10-01, release date: 2021-05-19, Last modification date: 2021-06-16) |
Primary citation | Fedry, J.,Hurdiss, D.L.,Wang, C.,Li, W.,Obal, G.,Drulyte, I.,Du, W.,Howes, S.C.,van Kuppeveld, F.J.M.,Forster, F.,Bosch, B.J. Structural insights into the cross-neutralization of SARS-CoV and SARS-CoV-2 by the human monoclonal antibody 47D11. Sci Adv, 7:-, 2021 Cited by PubMed Abstract: The emergence of SARS-CoV-2 antibody escape mutations highlights the urgent need for broadly neutralizing therapeutics. We previously identified a human monoclonal antibody, 47D11, capable of cross-neutralizing SARS-CoV-2 and SARS-CoV and protecting against the associated respiratory disease in an animal model. Here, we report cryo-EM structures of both trimeric spike ectodomains in complex with the 47D11 Fab. 47D11 binds to the closed receptor-binding domain, distal to the ACE2 binding site. The CDRL3 stabilizes the N343 glycan in an upright conformation, exposing a mutationally constrained hydrophobic pocket, into which the CDRH3 loop inserts two aromatic residues. 47D11 stabilizes a partially open conformation of the SARS-CoV-2 spike, suggesting that it could be used effectively in combination with other antibodies targeting the exposed receptor-binding motif. Together, these results reveal a cross-protective epitope on the SARS-CoV-2 spike and provide a structural roadmap for the development of 47D11 as a prophylactic or postexposure therapy for COVID-19. PubMed: 33958322DOI: 10.1126/sciadv.abf5632 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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