8G3N
N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI9 Fab molecules
Summary for 8G3N
Entry DOI | 10.2210/pdb8g3n/pdb |
Related | 8G3M |
EMDB information | 29704 29705 |
Descriptor | Neuraminidase, FNI9 Fab heavy chain, FNI9 Fab light chain, ... (8 entities in total) |
Functional Keywords | viral glycoprotein, antibody, fab, influenza, viral protein-immune system complex, viral protein/immune system |
Biological source | Influenza A virus More |
Total number of polymer chains | 12 |
Total formula weight | 425746.51 |
Authors | |
Primary citation | Momont, C.,Dang, H.V.,Zatta, F.,Hauser, K.,Wang, C.,di Iulio, J.,Minola, A.,Czudnochowski, N.,De Marco, A.,Branch, K.,Donermeyer, D.,Vyas, S.,Chen, A.,Ferri, E.,Guarino, B.,Powell, A.E.,Spreafico, R.,Yim, S.S.,Balce, D.R.,Bartha, I.,Meury, M.,Croll, T.I.,Belnap, D.M.,Schmid, M.A.,Schaiff, W.T.,Miller, J.L.,Cameroni, E.,Telenti, A.,Virgin, H.W.,Rosen, L.E.,Purcell, L.A.,Lanzavecchia, A.,Snell, G.,Corti, D.,Pizzuto, M.S. A pan-influenza antibody inhibiting neuraminidase via receptor mimicry. Nature, 618:590-597, 2023 Cited by PubMed Abstract: Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift and suboptimal immune responses. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses. PubMed: 37258672DOI: 10.1038/s41586-023-06136-y PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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