A core trimer of the paramyxovirus fusion protein: parallels to influenza virus hemagglutinin and HIV-1 gp41

Virology. 1998 Aug 15;248(1):20-34. doi: 10.1006/viro.1998.9242.


The paramyxovirus fusion (F) protein mediates membrane fusion. The biologically active F protein consists of a membrane distal subunit, F2, and a membrane-anchored subunit, F1. We have identified a highly stable structure composed of peptides derived from the F1 heptad repeat A, which abuts the hydrophobic fusion peptide (peptide N-1), and the F1 heptad repeat B, located 270 residues downstream and adjacent to the transmembrane domain (peptides C-1 and C-2). In isolation, peptide N-1 is 47% alpha-helical and peptide C-1 and C-2 are unfolded. When mixed together, peptides N1 + C1 form a thermostable (Tm >90 degreesC), 82% alpha-helical, discrete trimer of heterodimers (mass 31,300 Mr) that is resistant to denaturation by 2% SDS at 40 degreesC. We suggest that this alpha-helical trimeric complex represents the core most stable form of the F protein that either is fusion competent or forms after fusion has occurred. Peptide C-1 is a potent inhibitor of both the lipid mixing and the aqueous content mixing fusion activity of the SV5 F protein. In contrast, peptides N-1 and N-2 inhibit cytoplasmic content mixing but not lipid mixing, leading to a stable hemifusion state. Thus, these peptides define functionally different steps in the fusion process. The parallels among both the fusion processes and the protein structures of paramyxovirus F proteins, HIV gp41, and influenza virus hemagglutinin are discussed, as the analogies are indicative of a conserved paradigm for fusion promotion among fusion proteins from widely disparate viruses.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Fusion
  • Cell Line
  • Circular Dichroism
  • Erythrocytes / physiology
  • HIV Envelope Protein gp41 / chemistry*
  • HIV-1 / metabolism
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Respirovirus / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Thermodynamics
  • Viral Fusion Proteins / biosynthesis*
  • Viral Fusion Proteins / chemistry*


  • HIV Envelope Protein gp41
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Macromolecular Substances
  • Recombinant Proteins
  • Viral Fusion Proteins