7X6L

Cryo-EM structure of H3 hemagglutinin from A/HongKong/01/1968 in complex with a neutralizing antibody 28-12

7X6L の概要

• エントリーDOI: 10.2210/pdb7x6l/pdb
• EMDBエントリー: 33023
• 分子名称: Heavy chain of antibody 12 fab, The light chain of the antibody 12 fab, Hemagglutinin, ... (4 entities in total)
• 機能のキーワード: h3 hemagglutinin, a/hongkong/01/1968, antibody 28-12, cryo-em, structural protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 312741.77

構造登録者

Cong, Y.,Liu, C.X. (登録日: 2022-03-07, 公開日: 2022-03-23, 最終更新日: 2022-06-22)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.7 Å)