8FAW

Structure of Hemagglutinin from Influenza A/Victoria/22/2020 in complex with LSTC

8FAW の概要

• エントリーDOI: 10.2210/pdb8faw/pdb
• 関連するPDBエントリー: 8FAQ
• 分子名称: Hemagglutinin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: influenza a hemagglutinin, viral protein
• 由来する生物種: Influenza A virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57703.31

構造登録者

Hernandez Garcia, A.,Lei, R. (登録日: 2022-11-28, 公開日: 2024-06-19, 最終更新日: 2024-10-23)

主引用文献

Lei, R.,Liang, W.,Ouyang, W.O.,Hernandez Garcia, A.,Kikuchi, C.,Wang, S.,McBride, R.,Tan, T.J.C.,Sun, Y.,Chen, C.,Graham, C.S.,Rodriguez, L.A.,Shen, I.R.,Choi, D.,Bruzzone, R.,Paulson, J.C.,Nair, S.K.,Mok, C.K.P.,Wu, N.C.
Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin.
Nat Commun, 15:5175-5175, 2024

PubMed Abstract: The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.

PubMed: 38890325
DOI: 10.1038/s41467-024-49487-4

実験手法

X-RAY DIFFRACTION (2.16 Å)