title: Structural characterization of the hemagglutinin receptor specificity from the 2009 H1N1 influenza pandemic.
abstract: Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor-binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only for α2-6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For α2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with α2-6- and α2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for α2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus.
authors.affiliation: Department of Molecular Biology and Department of Chemical Physiology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Ryan
authors.initials: R
authors.lastname: McBride
authors.forename: Corwin M
authors.initials: CM
authors.lastname: Nycholat
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007251:Influenza, Human / Q000453:epidemiology / Q000378:metabolism / Q000821:virology; D008958:Models, Molecular; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D058873:Pandemics; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid
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