7UZ8
Structure of the SARS-CoV-2 Omicron BA.1 S 6P trimer in complex with the mouse antibody Fab fragment, M8a-31
Summary for 7UZ8
| Entry DOI | 10.2210/pdb7uz8/pdb |
| EMDB information | 26882 |
| Descriptor | Spike glycoprotein, M8a-31 Fab heavy chain, M8a-31 Fab light chain, ... (5 entities in total) |
| Functional Keywords | immune system, neutralizing antibody, immune system-viral protein complex, immune system/viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 571744.87 |
| Authors | Fan, C.,Bjorkman, P.J. (deposition date: 2022-05-08, release date: 2022-12-07, Last modification date: 2024-11-13) |
| Primary citation | Fan, C.,Cohen, A.A.,Park, M.,Hung, A.F.,Keeffe, J.R.,Gnanapragasam, P.N.P.,Lee, Y.E.,Gao, H.,Kakutani, L.M.,Wu, Z.,Kleanthous, H.,Malecek, K.E.,Williams, J.C.,Bjorkman, P.J. Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes. Immunity, 55:2419-, 2022 Cited by PubMed Abstract: Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs. PubMed: 36370711DOI: 10.1016/j.immuni.2022.10.019 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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