7X6O

Cryo-EM structure of H1 hemagglutinin from A/Washington/05/2011 in complex with a neutralizing antibody 28-12

Summary for 7X6O

• Entry DOI: 10.2210/pdb7x6o/pdb
• EMDB information: 33024
• Descriptor: Hemagglutinin, Heavy chain of antibody 12 fab, The light chain of antibody 12 fab, ... (4 entities in total)
• Functional Keywords: influenza a virus, h1n1, antibody 12 fab, cryo-em, viral protein
• Biological source: Influenza A virus; More
• Total number of polymer chains: 12
• Total formula weight: 314841.64

Authors

Cong, Y.,Liu, C.X. (deposition date: 2022-03-07, release date: 2022-03-23, Last modification date: 2024-10-30)

Primary citation

Sun, X.,Liu, C.,Lu, X.,Ling, Z.,Yi, C.,Zhang, Z.,Li, Z.,Jin, M.,Wang, W.,Tang, S.,Wang, F.,Wang, F.,Wangmo, S.,Chen, S.,Li, L.,Ma, L.,Zhang, Y.,Yang, Z.,Dong, X.,Qian, Z.,Ding, J.,Wang, D.,Cong, Y.,Sun, B.
Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus.
Nat Commun, 13:2378-2378, 2022

PubMed Abstract: Most structurally characterized broadly neutralizing antibodies (bnAbs) against influenza A viruses (IAVs) target the conserved conformational epitopes of hemagglutinin (HA). Here, we report a lineage of naturally occurring human antibodies sharing the same germline gene, V3-48/V1-12. These antibodies broadly neutralize the major circulating strains of IAV in vitro and in vivo mainly by binding a contiguous epitope of H3N2 HA, but a conformational epitope of H1N1 HA, respectively. Our structural and functional studies of antibody 28-12 revealed that the continuous amino acids in helix A, particularly N49 of H3 HA, are critical to determine the binding feature with 28-12. In contrast, the conformational epitope feature is dependent on the discontinuous segments involving helix A, the fusion peptide, and several HA1 residues within H1N1 HA. We report that this antibody was initially selected by H3 (group 2) viruses and evolved via somatic hypermutation to enhance the reactivity to H3 and acquire cross-neutralization to H1 (group 1) virus. These findings enrich our understanding of different antigenic determinants of heterosubtypic influenza viruses for the recognition of bnAbs and provide a reference for the design of influenza vaccines and more effective antiviral drugs.

PubMed: 35501328
DOI: 10.1038/s41467-022-29950-w

Experimental method

ELECTRON MICROSCOPY (3.5 Å)