A dual-functional paramyxovirus F protein regulatory switch segment: Activation and membrane fusion

Charles J. Russell, Karen L. Kantor, Theodore S. Jardetzky, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Many viral fusion-mediating glycoproteins couple α-helical bundle formation to membrane merger, but have different methods for fusion activation. To study paramyxovirus-mediated fusion, we mutated the SV5 fusion (F) protein at conserved residues L447 and 1449, which are adjacent to heptad repeat (HR) B and bind to a prominent cavity in the HRA trimeric coiled coil in the fusogenic six-helix bundle (6HB) structure. These analyses on residues L447 and 1449, both in intact F protein and in 6HB, suggest a metamorphic region around these residues with dual structural roles. Mutation of L447 and 1449 to aliphatic residues destabilizes the 6HB structure and attenuates fusion activity. Mutation of L447 and 1449 to aromatic residues also destabilizes the 6HB structure despite promoting hyperactive fusion, indicating that 6HB stability alone does not dictate fusogenicity. Thus, residues L447 and 1449 adjacent to HRB in paramyxovirus F have distinct roles in fusion activation and 6HB formation, suggesting this region is involved in a conformational switch.

Original languageEnglish (US)
Pages (from-to)363-374
Number of pages12
JournalJournal of Cell Biology
Volume163
Issue number2
DOIs
StatePublished - Oct 27 2003

Keywords

  • Antiviral agents
  • Membrane fusion activation
  • Molecular models
  • Protein conformation
  • Viral fusion proteins

ASJC Scopus subject areas

  • Cell Biology

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