title: The heads of the measles virus attachment protein move to transmit the fusion-triggering signal.
abstract: The measles virus entry system, consisting of attachment (hemagglutinin, H) and fusion proteins, operates by means of a variety of natural and targeted receptors; however, the mechanism that triggers fusion of the viral envelope with the plasma membrane is not understood. Here, we tested a model proposing that the two heads of an H dimer, which are covalently linked at their base, after binding two receptor molecules, move relative to each other to transmit the fusion-triggering signal. Indeed, stabilizing the H-dimer interface with additional intermolecular disulfide bonds prevented membrane fusion, an effect that was reversed by a reducing agent. Moreover, a membrane-anchored designated receptor efficiently triggered fusion, provided that it engaged the H dimer at locations proximal to where the natural receptors bind and distal to the H-dimer interface. We discuss how receptors may force H-protein heads to switch partners and transmit the fusion-triggering signal.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Chanakha K
authors.initials: CK
authors.lastname: Navaratnarajah
authors.forename: Numan
authors.initials: N
authors.lastname: Oezguen
authors.forename: Levi
authors.initials: L
authors.lastname: Rupp
authors.forename: Leah
authors.initials: L
authors.lastname: Kay
authors.forename: Vincent H J
authors.initials: VH
authors.lastname: Leonard
authors.forename: Werner
authors.initials: W
authors.lastname: Braun
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008457:Measles / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D014709:Vero Cells; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D004220:Disulfides; D006389:Hemagglutinins, Viral; D003545:Cysteine