5vag
Crystal structure of H7-specific antibody m826 in complex with the HA1 domain of hemagglutinin from H7N9 influenza virus
Structural highlights
FunctionR4NN21_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity).[RuleBase:RU003324][SAAS:SAAS008980_004_327643] Publication Abstract from PubMedThe 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 A) 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. A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.,Yu F, Song H, Wu Y, Chang SY, 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 LR, Song Y, Min JY, Golding H, Ji X, Lu L, Jiang S, Dimitrov DS, Ying T Cell Host Microbe. 2017 Oct 11;22(4):471-483.e5. doi: 10.1016/j.chom.2017.08.011., Epub 2017 Sep 28. PMID:28966056[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
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