5VAG

Crystal structure of H7-specific antibody m826 in complex with the HA1 domain of hemagglutinin from H7N9 influenza virus

Summary for 5VAG

• Entry DOI: 10.2210/pdb5vag/pdb
• Descriptor: Hemagglutinin, Light chain of antibody m826, Heavy chain of antibody m826, ... (5 entities in total)
• Functional Keywords: hemagglutinin, h7n9, immune system
• Biological source: Influenza A virus; More
• Cellular location: Host apical cell membrane ; Single-pass type I membrane protein . Virion membrane ; Single-pass type I membrane protein : R4NN21
• Total number of polymer chains: 3
• Total formula weight: 85349.31

Authors

Song, H.,Ying, T.,Ji, X. (deposition date: 2017-03-26, release date: 2017-12-20, Last modification date: 2024-11-13)

Primary citation

Yu, F.,Song, H.,Wu, Y.,Chang, S.Y.,Wang, L.,Li, W.,Hong, B.,Xia, S.,Wang, C.,Khurana, S.,Feng, Y.,Wang, Y.,Sun, Z.,He, B.,Hou, D.,Manischewitz, J.,King, L.R.,Song, Y.,Min, J.Y.,Golding, H.,Ji, X.,Lu, L.,Jiang, S.,Dimitrov, D.S.,Ying, T.
A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.
Cell Host Microbe, 22:471-483.e5, 2017

PubMed Abstract: The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.

PubMed: 28966056
DOI: 10.1016/j.chom.2017.08.011

Experimental method

X-RAY DIFFRACTION (1.9 Å)