title: Triggering the measles virus membrane fusion machinery.
abstract: Paramyxoviruses contain glycoprotein fusion machineries that mediate membrane merger for infection. The molecular framework and mechanistic principles governing receptor-induced triggering of the machinery remain unknown. Using measles virus (MeV) fusion complexes, we demonstrate that receptor binding to only one dimer of the tetrameric attachment protein (H) dimer-of-dimers induces fusion-protein (F) triggering; receptor binding and F triggering can be communicated across the dimer-dimer interface of H; and the physical integrity of the tetramer is maintained during fusion. The central MeV H ectodomain stalk region requires structural flexibility for activation of F, and alanine substitutions in this section, physical stress, or exposure of H to soluble ligands trigger conformational rearrangements in native H tetramers. Binding of soluble receptor to H is sufficient to initiate refolding of F, underscoring the physiological significance of this rearrangement of the H tetramer. These data outline a model of the triggering of the physiological MeV fusion machinery in which unilateral receptor binding to one dimer pair in the H tetramer is sufficient to induce a reorganization of H that affects the conformation of the central stalk section, severing interactions between H and the F trimer and activating refolding of F.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Brindley
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.forename: Philippe
authors.initials: P
authors.lastname: Plattet
authors.forename: Richard K
authors.initials: RK
authors.lastname: Plemper
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D019281:Dimerization; D008459:Measles virus / Q000502:physiology*; D008561:Membrane Fusion; D016297:Mutagenesis, Site-Directed; D063347:Native Polyacrylamide Gel Electrophoresis; D011487:Protein Conformation; D017510:Protein Folding; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D014764:Viral Proteins