title: Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.
abstract: Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.
authors.forename: V
authors.initials: V
authors.lastname: Carbone
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: J X
authors.initials: JX
authors.lastname: Huang
authors.forename: M A
authors.initials: MA
authors.lastname: Baker
authors.forename: C
authors.initials: C
authors.lastname: Ong
authors.forename: M A
authors.initials: MA
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Rockman
authors.forename: T
authors.initials: T
authors.lastname: Velkov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002642:Chick Embryo; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009981:Influenza B virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005585:Influenza in Birds / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus