8EBP

HMPV F dimer bound to RSV-199 Fab

Summary for 8EBP

• Entry DOI: 10.2210/pdb8ebp/pdb
• EMDB information: 27995
• Descriptor: Fusion glycoprotein F0, RSV-199 light chain protein, RSV-199 heavy chain protein (3 entities in total)
• Functional Keywords: human antibody, rsv and mpv fusion protein, complex cryo-em structure, biosynthetic protein, viral protein and antiviral protein
• Biological source: Human metapneumovirus A; More
• Total number of polymer chains: 6
• Total formula weight: 188710.94

Authors

Wen, X.,Jardetzky, T.S. (deposition date: 2022-08-31, 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

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: 37516111
DOI: 10.1016/j.chom.2023.07.002

Experimental method

ELECTRON MICROSCOPY (3.38 Å)