8CW9
Prefusion-stabilized hMPV fusion protein bound to ADI-61026 and MPE8 Fabs
Summary for 8CW9
| Entry DOI | 10.2210/pdb8cw9/pdb |
| EMDB information | 27024 |
| Descriptor | Fusion glycoprotein F0, MPE8 light chain, ADI-61026 heavy, ... (6 entities in total) |
| Functional Keywords | site 0 neutralizing antibody, prefusion-stabilized hmpv f protein, viral protein, viral protein-immune system complex, viral protein/immune system |
| Biological source | Human metapneumovirus More |
| Total number of polymer chains | 15 |
| Total formula weight | 541479.03 |
| Authors | Hsieh, C.-L.,McLellan, J.S. (deposition date: 2022-05-18, release date: 2022-08-10, Last modification date: 2024-10-30) |
| Primary citation | Rappazzo, C.G.,Hsieh, C.L.,Rush, S.A.,Esterman, E.S.,Delgado, T.,Geoghegan, J.C.,Wec, A.Z.,Sakharkar, M.,Mas, V.,McLellan, J.S.,Walker, L.M. Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein. Immunity, 55:1710-1724.e8, 2022 Cited by PubMed Abstract: Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens. PubMed: 35944529DOI: 10.1016/j.immuni.2022.07.003 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.46 Å) |
Structure validation
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