Structural basis for paramyxovirus-mediated membrane fusion

Mol Cell. 1999 Mar;3(3):309-19. doi: 10.1016/s1097-2765(00)80458-x.

Abstract

Paramyxoviruses are responsible for significant human mortality and disease worldwide, but the molecular mechanisms underlying their entry into host cells remain poorly understood. We have solved the crystal structure of a fragment of the simian parainfluenza virus 5 fusion protein (SV5 F), revealing a 96 A long coiled coil surrounded by three antiparallel helices. This structure places the fusion and transmembrane anchor of SV5 F in close proximity with a large intervening domain at the opposite end of the coiled coil. Six amino acids, potentially part of the fusion peptide, form a segment of the central coiled coil, suggesting that this structure extends into the membrane. Deletion mutants of SV5 F indicate that putative flexible tethers between the coiled coil and the viral membrane are dispensable for fusion. The lack of flexible tethers may couple a final conformational change in the F protein directly to the fusion of two bilayers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Crystallization
  • Dimerization
  • Electrons
  • Hydrogen Bonding
  • Ions
  • Membrane Fusion*
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Respirovirus / chemistry
  • Respirovirus / genetics
  • Respirovirus / metabolism*
  • Sequence Deletion
  • Viral Fusion Proteins / chemistry*
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / metabolism

Substances

  • Ions
  • Peptide Fragments
  • Viral Fusion Proteins

Associated data

  • PDB/1SVF