8G3P

N2 neuraminidase of A/Hong_Kong/2671/2019 in complex with 4 FNI9 Fab molecules

8G3P の概要

• エントリーDOI: 10.2210/pdb8g3p/pdb
• 関連するPDBエントリー: 8G3O
• EMDBエントリー: 29706 29707
• 分子名称: FNI9 Fab heavy chain, FNI9 Fab light chain, Neuraminidase, ... (7 entities in total)
• 機能のキーワード: viral glycoprotein, antibody, fab, influenza, virus, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 425078.06

構造登録者

Dang, H.V.,Snell, G. (登録日: 2023-02-08, 公開日: 2023-05-31, 最終更新日: 2024-10-16)

主引用文献

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

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

実験手法

ELECTRON MICROSCOPY (2.5 Å)