9EKF

CryoEM structure of H5N1 A/Texas/37/2024 HA bound to Fab 65C6 and an auto glycan occupying the receptor-binding site

9EKF の概要

• エントリーDOI: 10.2210/pdb9ekf/pdb
• EMDBエントリー: 48120
• 分子名称: Hemagglutinin, Fab 65C6 Heavy Chain, Fab 65C6 Light Chain, ... (5 entities in total)
• 機能のキーワード: h5n1, antibody, influenza, viral protein
• 由来する生物種: Influenza A virus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 351013.89

構造登録者

Morano, N.C.,Shapiro, L.,Kwong, P.D. (登録日: 2024-12-02, 公開日: 2024-12-18, 最終更新日: 2025-02-19)

主引用文献

Morano, N.C.,Guo, Y.,Becker, J.E.,Li, Z.,Yu, J.,Ho, D.D.,Shapiro, L.,Kwong, P.D.
Structure of a zoonotic H5N1 hemagglutinin reveals a receptor-binding site occupied by an auto-glycan.
Structure, 33:228-233.e3, 2025

PubMed Abstract: Highly pathogenic avian influenza has spilled into many mammals, most notably cows and poultry, with several dozen human breakthrough infections. Zoonotic crossovers, with hemagglutinins mutated to enhance viral ability to use human α2-6-linked sialic acid receptors versus avian α2-3-linked ones, highlight the pandemic risk. To gain insight into these crossovers, we determined the cryoelectron microscopy (cryo-EM) structure of the hemagglutinin from the zoonotic H5N1 A/Texas/37/2024 strain (clade 2.3.4.4b) in complex with a previously reported neutralizing antibody. Surprisingly, we found that the receptor-binding site of this H5N1 hemagglutinin was already occupied by an α2-3-linked sialic acid and that this glycan emanated from asparagine N169 of a neighboring protomer on hemagglutinin itself. This structure thus highlights recognition by influenza hemagglutinin of an "auto"-α2-3-linked sialic acid from N169, an N-linked glycan conserved in 95% of H5 strains, and adds "auto-glycan recognition," which may play a role in viral dispersal, to the complexities surrounding H5N1 zoonosis.

PubMed: 39884273
DOI: 10.1016/j.str.2025.01.001

実験手法

ELECTRON MICROSCOPY (2.68 Å)