9FM2
Cryo-EM structure of Influenza B/Washington/02/2019 virus neuraminidase in complex with single-domain antibody hVHH-525.
Summary for 9FM2
| Entry DOI | 10.2210/pdb9fm2/pdb |
| Related | 9FM1 |
| EMDB information | 50546 50547 |
| Descriptor | Single-domain antibody hVHH-525, Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | neuraminidase, single-domain antibody, complex, antiviral protein |
| Biological source | Lama glama More |
| Total number of polymer chains | 5 |
| Total formula weight | 228143.18 |
| Authors | Felix, J.,Matthys, A.,Savvides, S.N.,Saelens, X. (deposition date: 2024-06-05, release date: 2025-07-09, Last modification date: 2025-07-16) |
| Primary citation | Matthys, A.,Felix, J.,Catani, J.P.P.,Roose, K.,Nerinckx, W.,Van Buyten, B.,Fijalkowska, D.,Callewaert, N.,Savvides, S.N.,Saelens, X. Single-domain antibodies directed against hemagglutinin and neuraminidase protect against influenza B viruses. Nat Commun, 16:5831-5831, 2025 Cited by PubMed Abstract: Influenza B viruses are antigenically diverse and contribute significantly to the annual influenza burden. Here we report influenza B virus neutralizing single-domain antibodies that target highly conserved regions of the hemagglutinin and neuraminidase. Structural studies by single particle electron cryo-microscopy (cryo-EM) revealed that one of these single-domain antibodies prevents the conformational transition of the viral hemagglutinin to the post-fusion state by targeting a quaternary epitope spanning two protomers in the hemagglutinin-stem region. A second single-domain antibody broadly inhibits influenza B neuraminidase activity, including an oseltamivir-resistant neuraminidase, and its complex with neuraminidase elucidated by single particle cryo-EM established that it binds to residues in the neuraminidase catalytic site. Head-to-tail fusions of these single-domain antibodies led to bispecific binders that further improved the neutralization breadth and potency against influenza B viruses. These single-domain antibodies, fused to a human IgG1-Fc domain, fully protected female mice against an otherwise lethal influenza B virus challenge. Our findings underscore the potential of engineered single-domain antibodies to help control influenza B virus infections. PubMed: 40593518DOI: 10.1038/s41467-025-60232-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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