7FAH

Immune complex of head region of CA09 HA and neutralizing antibody 12H5

7FAH の概要

• エントリーDOI: 10.2210/pdb7fah/pdb
• 分子名称: Hemagglutinin, heavy chain of antibody 12H5, Light chain of antibody 12H5, ... (5 entities in total)
• 機能のキーワード: influenza virus, ha, receptor binding site, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Influenza A virus (strain swl A/California/04/2009 H1N1); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 218643.95

構造登録者

Li, T.T.,Xue, W.H.,Gu, Y.,Li, S.W. (登録日: 2021-07-06, 公開日: 2022-07-06, 最終更新日: 2024-10-30)

主引用文献

Li, T.,Chen, J.,Zheng, Q.,Xue, W.,Zhang, L.,Rong, R.,Zhang, S.,Wang, Q.,Hong, M.,Zhang, Y.,Cui, L.,He, M.,Lu, Z.,Zhang, Z.,Chi, X.,Li, J.,Huang, Y.,Wang, H.,Tang, J.,Ying, D.,Zhou, L.,Wang, Y.,Yu, H.,Zhang, J.,Gu, Y.,Chen, Y.,Li, S.,Xia, N.
Identification of a cross-neutralizing antibody that targets the receptor binding site of H1N1 and H5N1 influenza viruses.
Nat Commun, 13:5182-5182, 2022

PubMed Abstract: Influenza A viruses pose a significant threat globally each year, underscoring the need for a vaccine- or antiviral-based broad-protection strategy. Here, we describe a chimeric monoclonal antibody, C12H5, that offers neutralization against seasonal and pandemic H1N1 viruses, and cross-protection against some H5N1 viruses. Notably, C12H5 mAb offers broad neutralizing activity against H1N1 and H5N1 viruses by controlling virus entry and egress, and offers protection against H1N1 and H5N1 viral challenge in vivo. Through structural analyses, we show that C12H5 engages hemagglutinin (HA), the major surface glycoprotein on influenza, at a distinct epitope overlapping the receptor binding site and covering the 140-loop. We identified eight highly conserved (~90%) residues that are essential for broad H1N1 recognition, with evidence of tolerance for Asp or Glu at position 190; this site is a molecular determinant for human or avian host-specific recognition and this tolerance endows C12H5 with cross-neutralization potential. Our results could benefit the development of antiviral drugs and the design of broad-protection influenza vaccines.

PubMed: 36056024
DOI: 10.1038/s41467-022-32926-5

実験手法

X-RAY DIFFRACTION (3.151 Å)