9E69

Antibody 5E10

Summary for 9E69

• Entry DOI: 10.2210/pdb9e69/pdb
• Descriptor: Heavy chain of antibody 5E10, Light Chain of antibody 5E10, Heavy Chain of antibody 5E10, ... (4 entities in total)
• Functional Keywords: antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 99661.04

Authors

Zhou, T.,Sao-Fong Cheung, C.,Kwong, P.D. (deposition date: 2024-10-29, release date: 2025-07-16, Last modification date: 2026-02-04)

Primary citation

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, 33:1820-1830.e4, 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

Experimental method

X-RAY DIFFRACTION (2.63 Å)