Mso1p regulates membrane fusion through interactions with the putative N-peptide-binding area in Sec1p domain 1

Mol Biol Cell. 2010 Apr 15;21(8):1362-74. doi: 10.1091/mbc.e09-07-0546. Epub 2010 Feb 24.


Sec1p/Munc18 (SM) family proteins regulate SNARE complex function in membrane fusion through their interactions with syntaxins. In addition to syntaxins, only a few SM protein interacting proteins are known and typically, their binding modes with SM proteins are poorly characterized. We previously identified Mso1p as a Sec1p-binding protein and showed that it is involved in membrane fusion regulation. Here we demonstrate that Mso1p and Sec1p interact at sites of exocytosis and that the Mso1p-Sec1p interaction site depends on a functional Rab GTPase Sec4p and its GEF Sec2p. Random and targeted mutagenesis of Sec1p, followed by analysis of protein interactions, indicates that Mso1p interacts with Sec1p domain 1 and that this interaction is important for membrane fusion. In many SM family proteins, domain 1 binds to a N-terminal peptide of a syntaxin family protein. The Sec1p-interacting syntaxins Sso1p and Sso2p lack the N-terminal peptide. We show that the putative N-peptide binding area in Sec1p domain 1 is important for Mso1p binding, and that Mso1p can interact with Sso1p and Sso2p. Our results suggest that Mso1p mimics N-peptide binding to facilitate membrane fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Binding Sites
  • Membrane Fusion*
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Munc18 Proteins / chemistry*
  • Munc18 Proteins / metabolism*
  • Mutation / genetics
  • Peptides / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Stability
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Qa-SNARE Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spores, Fungal / cytology
  • Spores, Fungal / metabolism


  • MSO1 protein, S cerevisiae
  • Membrane Proteins
  • Munc18 Proteins
  • Peptides
  • Qa-SNARE Proteins
  • SEC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins