9EI8

Cryo-EM structure of 5E10 Fab in complex with H3 influenza Singapore 2016 HA trimer

9EI8 の概要

• エントリーDOI: 10.2210/pdb9ei8/pdb
• EMDBエントリー: 48078
• 分子名称: Hemagglutinin HA1, Hemagglutinin HA2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: ha, influenza, flu, n-term, h3, sing16, immune system
• 由来する生物種: Influenza A virus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 202538.34

構造登録者

Gorman, J.,Kwong, P.D. (登録日: 2024-11-25, 公開日: 2025-08-06, 最終更新日: 2025-11-19)

主引用文献

Rawi, R.,Morano, N.C.,Cheung, C.S.,Du, H.,Gorman, J.,Prabhakaran, M.,Becker, J.E.,Bylund, T.,Charaf, S.,Chen, X.,Lee, M.,Harris, D.R.,Olia, A.S.,Ou, L.,Wang, L.,Wang, S.,Zhang, B.,Kanekiyo, M.,McDermott, A.B.,Zhou, T.,Shapiro, L.,Kwong, P.D.
The N terminus of H3-influenza hemagglutinin as a site-of-vulnerability to neutralizing antibody.
Structure, 33:1820-, 2025

PubMed Abstract: The N terminus of the H3 subtype of influenza virus hemagglutinin is ∼10 residues longer than the N termini of most other hemagglutinins. As conserved, exposed, and linear regions may be good vaccine targets, we investigated the vaccine utility of the extended H3-N terminus. First, we identified antibody 5E10, for which structure and binding analyses revealed recognition of the H3-N terminus. Second, we immunized mice with immunogens incorporating the H3-N terminus, boosted with hemagglutinin trimer, and isolated antibodies from immunogen-elicited B cells that bound both H3-N terminus and hemagglutinin trimer. However, hemagglutinin-complex structures of two such antibodies, 3864-6 and 3864-10, that neutralized H3-influenza strains, revealed only peripheral recognition of the hemagglutinin N terminus. Collectively, these results reveal the N terminus of H3 hemagglutinin to be a suboptimal vaccine target and suggest that-in addition to being conserved, flexible, and accessible-other factors influence the elicitation of potent broadly neutralizing responses.

PubMed: 40816277
DOI: 10.1016/j.str.2025.07.015

実験手法

ELECTRON MICROSCOPY (3.83 Å)