EMD-27808

Single-particle
2.46 Å
EMD-27808 Deposition: 08/08/2022
Map released: 16/08/2023
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-27808

RSV F trimer bound to RSV-199 Fab

EMD-27808

Single-particle
2.46 Å
EMD-27808 Deposition: 08/08/2022
Map released: 16/08/2023
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human respiratory syncytial virus A2
Sample: RSV fusion protein complex with RSV-199 Fab
Fitted models: 8dzw (Avg. Q-score: 0.569)

Deposition Authors: Wen X, Jardetzky TS
Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved antibody recognition mode.
Wen X, Suryadevara N, Kose N, Liu J, Zhan X, Handal LS , Williamson LE, Trivette A, Carnahan RH, Jardetzky TS , Crowe Jr JE
(2023) Cell Host Microbe , 31 , 1288 - 1300.e6
PUBMED: 37516111
DOI: doi:10.1016/j.chom.2023.07.002
ISSN: 1934-6069
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.