4hkx
Influenza hemagglutinin in complex with CH67 Fab
Structural highlights
FunctionA7UPX0_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.[RuleBase:RU003324][SAAS:SAAS00145386] Publication Abstract from PubMedAffinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines. Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.,Schmidt AG, Xu H, Khan AR, O'Donnell T, Khurana S, King LR, Manischewitz J, Golding H, Suphaphiphat P, Carfi A, Settembre EC, Dormitzer PR, Kepler TB, Zhang R, Moody MA, Haynes BF, Liao HX, Shaw DE, Harrison SC Proc Natl Acad Sci U S A. 2012 Nov 21. PMID:23175789[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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