Autoinhibition of SNARE complex assembly by a conformational switch represents a conserved feature of syntaxins

Biochem Soc Trans. 2010 Feb;38(Pt 1):209-12. doi: 10.1042/BST0380209.

Abstract

Regulation and specificity of membrane trafficking are required to maintain organelle integrity while performing essential cellular transport. Membrane fusion events in all eukaryotic cells are facilitated by the formation of specific SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) complexes between proteins on opposing lipid bilayers. Although regulation of SNARE complex assembly is not well understood, it is clear that two conserved protein families, the Sx (syntaxin) and the SM (Sec1p/Munc18) proteins, are central to this process. Sxs are a subfamily of SNARE proteins; in addition to the coiled-coil SNARE motif, Sxs possess an N-terminal, autonomously folded, triple-helical (Habc) domain. For some Sxs, it has been demonstrated that this Habc domain exerts an autoinhibitory effect on SNARE complex assembly by making intramolecular contacts with the SNARE motif. SM proteins regulate membrane fusion through interactions with their cognate Sxs. One hypothesis for SM protein function is that they facilitate a switch of the Sx from a closed to an open conformation, thus lifting the inhibitory action of the Habc domain and freeing the SNARE motif to participate in SNARE complexes. However, whether these regulatory mechanisms are conserved throughout the Sx/SM protein families remains contentious as it is not clear whether the closed conformation represents a universal feature of Sxs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Munc18 Proteins / chemistry
  • Munc18 Proteins / metabolism
  • Protein Conformation*
  • Qa-SNARE Proteins / chemistry*
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism
  • SNARE Proteins / chemistry*
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Multiprotein Complexes
  • Munc18 Proteins
  • Qa-SNARE Proteins
  • SNARE Proteins
  • Saccharomyces cerevisiae Proteins
  • TLG2 protein, S cerevisiae