7YHK

Cryo-EM structure of the HA trimer of A/Beijing/262/1995(H1N1) in complex with neutralizing antibody 12H5

Summary for 7YHK

• Entry DOI: 10.2210/pdb7yhk/pdb
• EMDB information: 33831
• Descriptor: 12H5 light chain, 12H5 heavy chain, Hemagglutinin, ... (5 entities in total)
• Functional Keywords: influenza virus, hemagglutinin, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/Beijing/262/1995(H1N1)); More
• Total number of polymer chains: 3
• Total formula weight: 88640.76

Authors

Zheng, Q.,Li, S.,Li, T.,Xue, W.,Sun, H. (deposition date: 2022-07-13, release date: 2022-08-17, Last modification date: 2023-07-19)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.14 Å)