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8G3N

N2 neuraminidase of A/Tanzania/205/2010 H3N2 in complex with 4 FNI9 Fab molecules

Summary for 8G3N
Entry DOI10.2210/pdb8g3n/pdb
Related8G3M
EMDB information29704 29705
DescriptorNeuraminidase, FNI9 Fab heavy chain, FNI9 Fab light chain, ... (8 entities in total)
Functional Keywordsviral glycoprotein, antibody, fab, influenza, viral protein-immune system complex, viral protein/immune system
Biological sourceInfluenza A virus
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Total number of polymer chains12
Total formula weight425746.51
Authors
Dang, H.,Snell, G. (deposition date: 2023-02-08, release date: 2023-05-31, Last modification date: 2024-10-23)
Primary citationMomont, 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: 37258672
DOI: 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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