Vam3p structure reveals conserved and divergent properties of syntaxins

Nat Struct Biol. 2001 Mar;8(3):258-64. doi: 10.1038/85012.

Abstract

Syntaxins and Sec1/munc18 proteins are central to intracellular membrane fusion. All syntaxins comprise a variable N-terminal region, a conserved SNARE motif that is critical for SNARE complex formation, and a transmembrane region. The N-terminal region of neuronal syntaxin 1A contains a three-helix domain that folds back onto the SNARE motif forming a 'closed' conformation; this conformation is required for munc18-1 binding. We have examined the generality of the structural properties of syntaxins by NMR analysis of Vam3p, a yeast syntaxin essential for vacuolar fusion. Surprisingly, Vam3p also has an N-terminal three-helical domain despite lacking apparent sequence homology with syntaxin 1A in this region. However, Vam3p does not form a closed conformation and its N-terminal domain is not required for binding to the Sec1/munc18 protein Vps33p, suggesting that critical distinctions exist in the mechanisms used by syntaxins to govern different types of membrane fusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Surface / chemistry
  • Antigens, Surface / metabolism
  • Carrier Proteins*
  • Conserved Sequence*
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Membrane Fusion
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Qa-SNARE Proteins
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Structure-Activity Relationship
  • Syntaxin 1
  • Vesicular Transport Proteins*

Substances

  • Antigens, Surface
  • Carrier Proteins
  • Fungal Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Qa-SNARE Proteins
  • SSO1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Syntaxin 1
  • VAM3 protein, S cerevisiae
  • VPS33 protein, S cerevisiae
  • Vesicular Transport Proteins

Associated data

  • PDB/1HS7