9BT5

The crystal structure of the HA1 domain of hemagglutinin from A/Shanghai/02/2013 (H7N9) bound to H7-235 Fab

9BT5 の概要

• エントリーDOI: 10.2210/pdb9bt5/pdb
• 分子名称: Hemagglutinin, Monoclonal antibody H7-235 heavy chain, Monoclonal antibody H7-235 light chain, ... (6 entities in total)
• 機能のキーワード: antibody, influenza, hemagglutinin, immune system
• 由来する生物種: Influenza A virus (A/Shanghai/02/2013(H7N9)); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 145843.13

構造登録者

Buchman, C.D.,Dong, J.,Crowe, J.E. (登録日: 2024-05-14, 公開日: 2025-06-25, 最終更新日: 2025-07-23)

主引用文献

Gilchuk, I.M.,Dong, J.,Irving, R.P.,Buchman, C.D.,Armstrong, E.,Turner, H.L.,Li, S.,Ward, A.B.,Carnahan, R.H.,Crowe Jr., J.E.
Pan-H7 influenza human antibody virus neutralization depends on avidity and steric hindrance.
JCI Insight, 10:-, 2025

PubMed Abstract: H7N9 avian influenza virus is a zoonotic influenza virus of public health concern, with a 39% mortality rate in humans. H7N9-specific prevention or treatments for humans have not been approved. We previously isolated a human monoclonal antibody (mAb) designated H7-235 that broadly reacts to diverse H7 viruses and neutralizes H7N9 viruses in vitro. Here, we report the crystal structure of H7 HA1 bound to the fragment antigen-binding region (Fab) of recombinant H7-235 (rH7-235). The crystal structure revealed that rH7-235 recognizes residues near but outside of the receptor binding site (RBS). Nevertheless, the rH7-235 IgG potently inhibits hemagglutination mediated by H7N9 viruses due to avidity effect and Fc steric hindrance. This mAb prophylactically protects mice against weight loss and death caused by challenge with lethal H7N9 viruses in vivo. rH7-235 mAb neutralizing activity alone is sufficient for protection when used at a high dose in a prophylactic setting. This study provides insights into mechanisms of viral neutralization by protective, broadly reactive anti-H7 antibodies, informing the rational design of therapeutics and vaccines against H7N9 influenza virus.

PubMed: 40471690
DOI: 10.1172/jci.insight.186182

実験手法

X-RAY DIFFRACTION (2.5 Å)