title: Activation of a paramyxovirus fusion protein is modulated by inside-out signaling from the cytoplasmic tail.
abstract: Many viruses have evolved fusion-mediating glycoproteins that couple the energy released from irreversible protein refolding to the work of membrane fusion. The viral fusion proteins require a triggering event to undergo a cascade of tightly regulated conformational changes. Different isolates of the paramyxovirus SV5 fusion (F) protein have either a short (20-residue) or long (42-residue) cytoplasmic tail (CT), and a long CT suppresses fusion activity in a sequence-specific manner. Addition of a domain to the F protein CT, which has the propensity to form a three-helix bundle, stabilizes the F protein and increases the energy required for fusion activation. Quantitative cell-cell fusion assays and measurement of ectodomain conformation by monoclonal antibody reactivity indicate that this suppression of fusion by the long CT or addition of a three-helix bundle occurs at a step preceding initial membrane merger. The data suggest that F protein activation involves CT signaling to the ectodomain.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Waning
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Russell
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D006224:Cricetinae; D003593:Cytoplasm; D015726:Giant Cells; D006801:Humans; D007668:Kidney; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins