9FM2

Cryo-EM structure of Influenza B/Washington/02/2019 virus neuraminidase in complex with single-domain antibody hVHH-525.

9FM2 の概要

• エントリーDOI: 10.2210/pdb9fm2/pdb
• 関連するPDBエントリー: 9FM1
• EMDBエントリー: 50546 50547
• 分子名称: Single-domain antibody hVHH-525, Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: neuraminidase, single-domain antibody, complex, antiviral protein
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 228143.18

構造登録者

Felix, J.,Matthys, A.,Savvides, S.N.,Saelens, X. (登録日: 2024-06-05, 公開日: 2025-07-09, 最終更新日: 2025-07-16)

主引用文献

Matthys, A.,Felix, J.,Catani, J.P.P.,Roose, K.,Nerinckx, W.,Van Buyten, B.,Fijalkowska, D.,Callewaert, N.,Savvides, S.N.,Saelens, X.
Single-domain antibodies directed against hemagglutinin and neuraminidase protect against influenza B viruses.
Nat Commun, 16:5831-5831, 2025

PubMed Abstract: Influenza B viruses are antigenically diverse and contribute significantly to the annual influenza burden. Here we report influenza B virus neutralizing single-domain antibodies that target highly conserved regions of the hemagglutinin and neuraminidase. Structural studies by single particle electron cryo-microscopy (cryo-EM) revealed that one of these single-domain antibodies prevents the conformational transition of the viral hemagglutinin to the post-fusion state by targeting a quaternary epitope spanning two protomers in the hemagglutinin-stem region. A second single-domain antibody broadly inhibits influenza B neuraminidase activity, including an oseltamivir-resistant neuraminidase, and its complex with neuraminidase elucidated by single particle cryo-EM established that it binds to residues in the neuraminidase catalytic site. Head-to-tail fusions of these single-domain antibodies led to bispecific binders that further improved the neutralization breadth and potency against influenza B viruses. These single-domain antibodies, fused to a human IgG1-Fc domain, fully protected female mice against an otherwise lethal influenza B virus challenge. Our findings underscore the potential of engineered single-domain antibodies to help control influenza B virus infections.

PubMed: 40593518
DOI: 10.1038/s41467-025-60232-3

実験手法

ELECTRON MICROSCOPY (3.6 Å)