8TW3

hMPV fusion protein complexed with single domain antibodies sdHMPV16 and sdHMPV12

Summary for 8TW3

• Entry DOI: 10.2210/pdb8tw3/pdb
• Descriptor: Single domain antibody sdHMPV12, Single domain antibody sdHMPV16, Fusion glycoprotein, ... (4 entities in total)
• Functional Keywords: metapneumovirus, fusion protein, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Lama glama (llama); More
• Total number of polymer chains: 6
• Total formula weight: 201491.20

Authors

Rush, S.A.,McLellan, J.S. (deposition date: 2023-08-19, release date: 2024-01-24, Last modification date: 2024-10-16)

Primary citation

Ballegeer, M.,van Scherpenzeel, R.C.,Delgado, T.,Iglesias-Caballero, M.,Garcia Barreno, B.,Pandey, S.,Rush, S.A.,Kolkman, J.A.,Mas, V.,McLellan, J.S.,Saelens, X.
A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein.
Mbio, 15:e0212223-e0212223, 2024

PubMed Abstract: Human metapneumovirus (hMPV) is an important respiratory pathogen for which no licensed antivirals or vaccines exist. Single-domain antibodies represent promising antiviral biologics that can be easily produced and formatted. We describe the isolation and detailed characterization of two hMPV-neutralizing single-domain antibodies that are directed against the fusion protein F. One of these single-domain antibodies broadly neutralizes hMPV A and B strains, can prevent proteolytic maturation of F, and binds to an epitope in the F trimer interface. This suggests that hMPV pre-F undergoes trimer opening or "breathing" on infectious virions, exposing a vulnerable site for neutralizing antibodies. Finally, we show that this single-domain antibody, fused to a human IgG1 Fc, can protect cotton rats against hMPV replication, an important finding for potential future clinical applications.

PubMed: 38117059
DOI: 10.1128/mbio.02122-23

Experimental method

X-RAY DIFFRACTION (2.9 Å)