title: Role of the hemagglutinin-neuraminidase protein in the mechanism of paramyxovirus-cell membrane fusion.
abstract: Paramyxovirus infects cells by initially attaching to a sialic acid-containing cellular receptor and subsequently fusing with the plasma membrane of the cells. Hemagglutinin-neuraminidase (HN) protein, which is responsible for virus attachment, interacts with the fusion protein in a virus type-specific manner to induce efficient membrane fusion. To elucidate the mechanism of HN-promoted membrane fusion, we characterized a series of Newcastle disease virus HN proteins whose surface residues were mutated. Fusion promotion activity was substantially altered in only the HN proteins with a mutation in the first or sixth beta sheet. These regions overlap the large hydrophobic surface of HN; thus, the hydrophobic surface may contain the fusion promotion domain. Furthermore, a comparison of the HN structure crystallized alone or in complex with 2-deoxy-2,3-dehydro-N-acetylneuraminic acid revealed substantial conformational changes in several loops within or near the hydrophobic surface. Our results suggest that the binding of HN protein to the receptor induces the conformational change of residues near the hydrophobic surface of HN protein and that this change triggers the activation of the F protein, which initiates membrane fusion.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA. toru.takimoto@stjude.org
authors.forename: Toru
authors.initials: T
authors.lastname: Takimoto
authors.forename: Garry L
authors.initials: GL
authors.lastname: Taylor
authors.forename: Helen C
authors.initials: HC
authors.lastname: Connaris
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Crennell
authors.forename: Allen
authors.initials: A
authors.lastname: Portner
mesh_terms: D019281:Dimerization; D015707:HN Protein / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D009522:Newcastle disease virus / Q000502:physiology*; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000502:physiology
chemical_list: D015707:HN Protein; D014760:Viral Fusion Proteins