Summary for 8DZW
| Entry DOI | 10.2210/pdb8dzw/pdb |
| EMDB information | 27808 |
| Descriptor | RSV fusion protein, RSV-199 Light chain protein, RSV-199 Heavy chain protein (3 entities in total) |
| Functional Keywords | human antibodies, rsv and mpv fusion protein, complex cryo-em structure, viral protein and antiviral protein, structural protein |
| Biological source | Human respiratory syncytial virus A2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 302315.70 |
| Authors | Wen, X.,Jardetzky, T.S. (deposition date: 2022-08-08, release date: 2023-08-16, Last modification date: 2024-11-13) |
| Primary citation | Wen, X.,Suryadevara, N.,Kose, N.,Liu, J.,Zhan, X.,Handal, L.S.,Williamson, L.E.,Trivette, A.,Carnahan, R.H.,Jardetzky, T.S.,Crowe Jr., J.E. Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved antibody recognition mode. Cell Host Microbe, 31:1288-1300.e6, 2023 Cited by PubMed Abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199. PubMed: 37516111DOI: 10.1016/j.chom.2023.07.002 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.46 Å) |
Structure validation
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