The heads of the measles virus attachment protein move to transmit the fusion-triggering signal

Nat Struct Mol Biol. 2011 Feb;18(2):128-34. doi: 10.1038/nsmb.1967. Epub 2011 Jan 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Chlorocebus aethiops
  • Cysteine / genetics
  • Cysteine / metabolism
  • Disulfides / metabolism
  • Hemagglutinins, Viral / chemistry*
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / metabolism*
  • Measles / virology*
  • Measles virus / genetics
  • Measles virus / physiology*
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Vero Cells
  • Virus Attachment*
  • Virus Internalization*

Substances

  • Disulfides
  • Hemagglutinins, Viral
  • Cysteine