title: An oligosaccharide at the C-terminus of the F-specific domain in the stalk of the human parainfluenza virus 3 hemagglutinin-neuraminidase modulates fusion.
abstract: The promotion of membrane fusion by the fusion (F) protein of human parainfluenza virus 3 (hPIV3) is dependent on a virus-specific contribution from the hemagglutinin-neuraminidase (HN) protein. By evaluation of chimeric hPIV3-Newcastle disease virus (NDV) HN proteins, we have previously shown that hPIV3-F-specificity is determined by a domain that extends from the middle of the membrane anchor to the 82nd residue in the ectodomain [Virology 209, (1995) 457; Arch. Virol. 13 (1997) 115]. If the corresponding NDV-derived residues replace the two C-terminal residues in this domain, no fusion is detected. However, these substitutions restore a glycosylation site present in NDV HN, but not in hPIV3 HN. Deletion of this site from a nested set of chimeras with hPIV3-derived N-terminal portions of decreasing length partially restores fusion, suggesting that an oligosaccharide near the top of hPIV3 HN stalk modulates fusion. In addition, further mutational analyses show that a chimera with only 125 N-terminal hPIV3-derived residues (72 in the stalk) actually promotes fusion more efficiently than the wt protein. These findings localize the C-terminus of the F-specific domain in hPIV3 HN a full 10 residues closer to the membrane than previously shown.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts, 55 Lake Avenue North, 0165-0122, Worcester, MA, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Wang
authors.forename: Anne M
authors.initials: AM
authors.lastname: Mirza
authors.forename: Jianrong
authors.initials: J
authors.lastname: Li
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mahon
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Iorio
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006031:Glycosylation; D015707:HN Protein / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008561:Membrane Fusion; D009522:Newcastle disease virus / Q000235:genetics; D009844:Oligosaccharides; D010224:Parainfluenza Virus 3, Human / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014760:Viral Fusion Proteins / Q000378:metabolism / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology
chemical_list: D015707:HN Protein; D009844:Oligosaccharides; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C072983:F protein, parainfluenza virus 3