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8tw3

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hMPV fusion protein complexed with single domain antibodies sdHMPV16 and sdHMPV12

Structural highlights

8tw3 is a 6 chain structure with sequence from Human metapneumovirus A and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein.,Ballegeer M, van Scherpenzeel RC, Delgado T, Iglesias-Caballero M, Garcia Barreno B, Pandey S, Rush SA, Kolkman JA, Mas V, McLellan JS, Saelens X mBio. 2024 Jan 16;15(1):e0212223. doi: 10.1128/mbio.02122-23. Epub 2023 Dec 20. PMID:38117059^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ballegeer M, van Scherpenzeel RC, Delgado T, Iglesias-Caballero M, García Barreno B, Pandey S, Rush SA, Kolkman JA, Mas V, McLellan JS, Saelens X. A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein. mBio. 2024 Jan 16;15(1):e0212223. PMID:38117059 doi:10.1128/mbio.02122-23