title: Binding of the influenza A virus to cell-surface receptors: structures of five hemagglutinin-sialyloligosaccharide complexes determined by X-ray crystallography.
abstract: The structures of five complexes of the X-31 influenza A (H3N2) virus hemagglutinin with sialyloligosaccharide receptor analogs have been determined from 2.5 to 2.8 A resolution by X-ray crystallography. There is well-defined electron density for three to five saccharides in all five complexes and a striking conformational difference between two linear pentasaccharides with the same composition but different linkage [alpha(2-->6) or alpha(2-->3)] at the terminal sialic acid. The bound position of the terminal sialic acid (NeuAc) is the same in all five complexes and is identical to that reported previously from the study of mono- and trisaccharides. The two oligosaccharides with NeuAc alpha(2-->6)Gal linkages and GlcNAc at the third position have a folded conformation with the GlcNAc doubled back to contact the sialic acid. The pentasaccharide with a terminal NeuAc alpha(2-->3)Gal linkage and GlcNAc at the third position has an extended (not folded) conformation and exits from the opposite side of the binding site than the alpha(2-->6)-linked molecule of the same composition. The difference between the conformation of the pentasaccharide with a 2,6 linkage and the trisaccharide 2,6-sialyllactose suggests that 2,6-sialyllactose is not, as previously believed, an appropriate analog of natural influenza A virus receptors. The oligosaccharides studied are NeuAc alpha(2-->3)Gal beta(1-->4)Glc, NeuAc alpha(2-->6)Gal beta(1-->4)Glc, NeuAc alpha(2-->3)Gal beta(1-->3)GlcNAc beta(1-->3)Gal beta(1-->4)Glc, NeuAc alpha(2-->6)Gal beta(1-->4)GlcNAc beta(1-->3)Gal beta(1-->4)Glc, and [NeuAc alpha(2-->6)Gal beta(1-->4)GlcNAc]2 beta(1-->3/6)Gal-beta-O-(CH2)5-COOCH3.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Eisen
authors.forename: S
authors.initials: S
authors.lastname: Sabesan
authors.forename: J J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism*; D009980:Influenza A virus / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C016735:sialooligosaccharides; C028583:sialyloligosaccharide receptor