title: Membrane environment can enhance the interaction of glycan binding protein to cell surface glycan receptors.
abstract: The binding of lectins to glycan receptors on the host cell surface is a key step contributing to the virulence and species specificity of most viruses. This is exemplified by the viral protein hemagglutinin (HA) of the influenza A virus, whose binding specificity is modulated by the linkage pattern of terminal sialic acids on glycan receptors of host epithelial cells. Such specificity dictates whether transmission is confined to a particular animal species or jumps between species. Here, we show, using H5N1 avian influenza as a model, that the specific binding of recombinant HA to α2-3 linked sialic acids can be enhanced dramatically by interaction with the surface of the lipid membrane. This effect can be quantitatively accounted for by a two-stage process in which weak association of HA with the membrane surface precedes more specific and tighter binding to the glycan receptor. The weak protein-membrane interaction discovered here in the model system may play an important secondary role in the infection and pathogenesis of the influenza A virus.
authors.affiliation: Department of Chemistry, Columbia University , New York, New York 10027, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Yini
authors.initials: Y
authors.lastname: Wang
authors.forename: Chia-I
authors.initials: CI
authors.lastname: Lin
authors.forename: Hung-wen
authors.initials: HW
authors.lastname: Liu
authors.forename: Athena
authors.initials: A
authors.lastname: Guo
authors.forename: X-Y
authors.initials: XY
authors.lastname: Zhu
mesh_terms: D060833:Cellular Microenvironment; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D011956:Receptors, Cell Surface