9CYJ

Cryo-EM structure of FNI9 IgG in complex with influenza virus neuraminidase from A/Kansas/14/2017 (H3N2)

Summary for 9CYJ

• Entry DOI: 10.2210/pdb9cyj/pdb
• EMDB information: 46046
• Descriptor: Neuraminidase, FNI9 IgG heavy chain, FNI9 IgG light chain, ... (9 entities in total)
• Functional Keywords: neuraminidase, hydrolase, antibody complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 6
• Total formula weight: 269151.94

Authors

Jo, G.,Han, J.,Torres, J.L.,Ferguson, J.A.,Ward, A.B. (deposition date: 2024-08-02, release date: 2025-08-13)

Primary citation

Jo, G.,Yamayoshi, S.,Ma, K.M.,Swanson, O.,Torres, J.L.,Ferguson, J.A.,Fernandez-Quintero, M.L.,Huang, J.,Copps, J.,Rodriguez, A.J.,Steichen, J.M.,Kawaoka, Y.,Han, J.,Ward, A.B.
Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3.
Nat Commun, 16:7067-7067, 2025

PubMed Abstract: Influenza viruses evolve rapidly, driving seasonal epidemics and posing global pandemic threats. While neuraminidase (NA) has emerged as a vaccine target, shared molecular features of NA antibody responses are still not well understood. Here, we describe cryo-electron microscopy structures of the broadly protective human antibody DA03E17, which was previously identified from an H1N1-infected donor, in complex with NA from A/H1N1, A/H3N2, and B/Victoria-lineage viruses. DA03E17 targets the highly conserved NA active site using its long CDR H3, which features a DR (Asp-Arg) motif that engages catalytic residues and mimics sialic acid interactions. We further demonstrate that this motif is conserved among several NA active site-targeting antibodies, indicating a common receptor mimicry strategy. We also identified BCR sequences containing this DR motif across all donors in a healthy human repertoire database, suggesting that such precursors may be relatively common and have vaccine targeting potential. Our findings reveal shared molecular features in NA active site-targeting antibodies that can be harnessed to design broad, immune-focused influenza vaccines.

PubMed: 40750588
DOI: 10.1038/s41467-025-62174-2

Experimental method

ELECTRON MICROSCOPY (2.97 Å)