9O4N
Cryo-EM structure of CR12042 Fab in complex with influenza virus neuraminidase from A/California/07/2009 (H1N1)
Summary for 9O4N
| Entry DOI | 10.2210/pdb9o4n/pdb |
| EMDB information | 70108 |
| Descriptor | Neuraminidase, CR12042 heavy chain, CR12042 light chain, ... (6 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 (A/California/07/2009(H1N1)) More |
| Total number of polymer chains | 12 |
| Total formula weight | 320553.16 |
| Authors | |
| 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 Cited by 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: 40750588DOI: 10.1038/s41467-025-62174-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.48 Å) |
Structure validation
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