7U8J

Crystal structure of chimeric hemagglutinin cH4/3 in complex with broad protective antibody 31.a.83

7U8J の概要

• エントリーDOI: 10.2210/pdb7u8j/pdb
• 分子名称: Hemagglutinin HA1 subunit, Hemagglutinin HA2 subunit, Antibody Fab light chain, ... (4 entities in total)
• 機能のキーワード: universal vaccine design, chimeric influenza hemagglutinin, ha trimer interface and stem, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Influenza A virus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 104591.69

構造登録者

Zhu, X.,Wilson, I.A. (登録日: 2022-03-08, 公開日: 2022-06-08, 最終更新日: 2024-10-23)

主引用文献

Zhu, X.,Han, J.,Sun, W.,Puente-Massaguer, E.,Yu, W.,Palese, P.,Krammer, F.,Ward, A.B.,Wilson, I.A.
Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface.
Proc.Natl.Acad.Sci.USA, 119:e2200821119-e2200821119, 2022

PubMed Abstract: Influenza virus hemagglutinin (HA) has been the primary target for influenza vaccine development. Broadly protective antibodies targeting conserved regions of the HA unlock the possibility of generating universal influenza immunity. Two group 2 influenza A chimeric HAs, cH4/3 and cH15/3, were previously designed to elicit antibodies to the conserved HA stem. Here, we show by X-ray crystallography and negative-stain electron microscopy that a broadly protective antistem antibody can stably bind to cH4/3 and cH15/3 HAs, thereby validating their potential as universal vaccine immunogens. Furthermore, flexibility was observed in the head domain of the chimeric HA structures, suggesting that antibodies could also potentially interact with the head interface epitope. Our structural and binding studies demonstrated that a broadly protective antihead trimeric interface antibody could indeed target the more open head domain of the cH15/3 HA trimer. Thus, in addition to inducing broadly protective antibodies against the conserved HA stem, chimeric HAs may also be able to elicit antibodies against the conserved trimer interface in the HA head domain, thereby increasing the vaccine efficacy.

PubMed: 35594401
DOI: 10.1073/pnas.2200821119

実験手法

X-RAY DIFFRACTION (4.9 Å)