9MQV

Crystal structure of human 1122A11 Fab in complex with influenza virus neuraminidase from A/Singapore/INFIMH-16-0019/2016 (H3N2)

9MQV の概要

• エントリーDOI: 10.2210/pdb9mqv/pdb
• 分子名称: Neuraminidase, 1122A11 FAB IGG1 HEAVY CHAIN, 1122A11 FAB LAMBDA LIGHT CHAIN, ... (9 entities in total)
• 機能のキーワード: hydrolase, immune system, influenza virus, neuraminidase, neutralization, substrate mimicry, viral protein, hydrolase-immune system complex, hydrolase/immune system
• 由来する生物種: Influenza A virus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 94972.20

構造登録者

Zhu, X.,Wilson, I.A. (登録日: 2025-01-06, 公開日: 2025-07-23, 最終更新日: 2026-01-21)

主引用文献

Zhu, X.,Khalil, A.M.,Piepenbrink, M.S.,Yu, W.,Ma, Y.,Martinez-Sobrido, L.,Wilson, I.A.,Kobie, J.J.
Structure and function of a cross-neutralizing influenza neuraminidase antibody that accommodates recent N2 NA Asn245 glycosylation.
Commun Biol, 8:1427-1427, 2025

PubMed Abstract: Monoclonal antibodies (mAbs) that recognize and inhibit a diverse range of influenza viruses, although relatively rare, have been isolated following infection or vaccination. Study of their ontology and mechanisms of action informs universal vaccine and therapeutic development. We have previously described a potent and broad neuraminidase (NA)-neutralizing human mAb, 1122A11, that neutralizes a wide range of H3N2 viruses. Here, further characterization of 1122A11 reveals reactivity to cross-group influenza A virus NAs, including group-1 N1 and N8, and group-2 N2 and N3 NAs. Recent H3N2 viruses have acquired Asn245 glycosylation on the active site rim. Crystal structures of an N2 NA from A/Singapore/INFIMH-16-0019/2016 (H3N2) at 2.3 Å (apo) and 2.2 Å (Fab bound) resolution showed that 1122A11 binding causes local changes to the periphery of NA active site to accommodate the glycan. The CDRH3 of 1122A11 inserts into the active site and mimics the substrate sialic acid. We then determined that the ability of 1122A11 to protect from lethal challenge in mice is not dependent on Fc-effector function. These results highlight the therapeutic potential of 1122A11 as a broad protective anti-viral and reinforce pursuit of immunogen development of NA antibodies toward achieving more universal influenza protection.

PubMed: 41053391
DOI: 10.1038/s42003-025-08830-1

実験手法

X-RAY DIFFRACTION (2.2 Å)