9C22

Crystal structure of chimeric hemagglutinin cH11/1 in complex with broad protective antibody 3E1

9C22 の概要

• エントリーDOI: 10.2210/pdb9c22/pdb
• 分子名称: Hemagglutinin, Antibody 3E1 Fab light chain, Antibody 3E1 Fab heavy chain, ... (6 entities in total)
• 機能のキーワード: 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: 24
• 化学式量合計: 963888.49

構造登録者

Nguyen, T.K.Y.,Wilson, I.A. (登録日: 2024-05-30, 公開日: 2025-05-07, 最終更新日: 2025-05-28)

主引用文献

Nguyen, Y.T.K.,Zhu, X.,Han, J.,Rodriguez, A.J.,Sun, W.,Yu, W.,Palese, P.,Krammer, F.,Ward, A.B.,Wilson, I.A.
Structural characterization of influenza group 1 chimeric hemagglutinins as broad vaccine immunogens.
Proc.Natl.Acad.Sci.USA, 122:e2416628122-e2416628122, 2025

PubMed Abstract: Chimeric hemagglutinins (cHA) appear to be promising for the design and development of universal influenza vaccines. Influenza A group 1 cHAs, cH5/1, cH8/1, and cH11/1, comprising an H1 stem attached to either an H5, H8, or H11 globular head, have been used sequentially as vaccine immunogens in human clinical trials and induced high levels of broadly protective antibodies. Using X-ray crystallography and negative-stain electron microscopy, we determined structures of cH5/1, cH8/1, and cH11/1 HAs in their apo (unliganded) and antibody Fab-bound states. Stem-reactive antibodies 3E1 and 31.b.09 recognize their cognate epitopes in cH5/1, cH8/1, and cH11/1 HAs. However, with cH5/1, the head domains are rotated by 35 to 45° around the threefold axis of the HA trimer compared to native HA with a more splayed-open conformation at the stem base. cH11/1 with 3E1 is structurally more native-like but resembles cH5/1 with 31.b.09, whereas cH8/1 with 31.b.09 exhibited a range of closed-to-open stem configurations with some separation of head and stem domains. Furthermore, all of these group 1 cHAs effectively bound a broad head trimer interface antibody and other broad stem antibodies. Thus, the cHAs exhibit structural plasticity without compromising the stem and head trimer interface epitopes for elicitation of influenza A group 1 cross-reactive antibodies.

PubMed: 39937865
DOI: 10.1073/pnas.2416628122

実験手法

X-RAY DIFFRACTION (4.6 Å)