4gms | pdb_00004gms

Crystal structure of heterosubtypic Fab S139/1 in complex with influenza A H3 hemagglutinin

spinqualitylabelsall models 4gms, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gms is a 12 chain structure with sequence from I75a3 and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, GOL, MAN, NAG, PG4, SO4 NonStd Res: PCA Related: 4gmt Gene: HA (I75A3) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HEMA_I75A3] 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. Publication Abstract from PubMed Continual and rapid mutation of seasonal influenza viruses by antigenic drift necessitates the almost annual reformulation of flu vaccines, which may offer little protection if the match to the dominant circulating strain is poor. S139/1 is a cross-reactive antibody that neutralizes multiple HA strains and subtypes, including those from H1N1 and H3N2 viruses that currently infect humans. The crystal structure of the S139/1 Fab in complex with the HA from the A/Victoria/3/1975 (H3N2) virus reveals that the antibody targets highly conserved residues in the receptor binding site and contacts antigenic sites A, B, and D. Binding and plaque reduction assays show that the monovalent Fab alone can protect against H3 strains, but the enhanced avidity from binding of bivalent IgG increases the breadth of neutralization to additional strains from the H1, H2, H13, and H16 subtypes. Thus, antibodies making relatively low affinity Fab interactions with the receptor binding site can have significant antiviral activity when enhanced by avidity through bivalent interactions of the IgG, thereby extending the breadth of binding and neutralization to highly divergent influenza virus strains and subtypes. Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity.,Lee PS, Yoshida R, Ekiert DC, Sakai N, Suzuki Y, Takada A, Wilson IA Proc Natl Acad Sci U S A. 2012 Oct 1. PMID:23027945 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hemagglutinin 3D structures

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