The paramyxovirus fusion protein forms an extremely stable core trimer: Structural parallels to influenza virus haemagglutinin and HIV-1 gp41

Robert A. Lamb*, Sangeeta Bagai Joshi, Rebecca Ellis Dutch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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. A highly stable structure has been identified comprised of peptides derived from the simian virus 5 (SV5) F1 heptad repeat A, which abuts the hydrophobic fusion peptide (peptide N-1), and the SV5 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% α-helical and peptide C-1 and C-2 are unfolded. When mixed together, peptides N1+C1 form a thermostable (T(m) > 90°C), 82% α-helical, discrete trimer of heterodimers (mass 31,300 M(r)) that is resistant to denaturation by 2% SDS at 40°C. The authors suggest that this α-helical trimeric complex represents the core most stable form of the F protein that is either fusion competent or forms after fusion has occurred. Peptide C-1 is a potent inhibitor of both the lipid mixing and aqueous content mixing fusion activity of the SV5 F protein. In contrast, peptide N-1 inhibits 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 haemagglutinin are discussed, as the analogies are indicative of a conserved paradigm for fusion promotion among fusion proteins from widely disparate viruses.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalMolecular Membrane Biology
Volume16
Issue number1
DOIs
StatePublished - 1999

Keywords

  • Fusion
  • Membranes
  • Paramyxovirus
  • Peptides
  • Viruses

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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