Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming

Nat Struct Mol Biol. 2015 Jul;22(7):547-54. doi: 10.1038/nsmb.3038. Epub 2015 Jun 1.


UNC-13-Munc13s have a central function in synaptic-vesicle priming through their MUN domains. However, it is unclear whether this function arises from the ability of the MUN domain to mediate the transition from the Munc18-1-closed syntaxin-1 complex to the SNARE complex in vitro. The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by α-helical bundles, with a highly conserved hydrophobic pocket in the middle. Mutation of two residues (NF) in this pocket abolishes the stimulation caused by the Munc13-1 MUN domain on SNARE-complex assembly and on SNARE-dependent proteoliposome fusion in vitro. Moreover, the same mutation in UNC-13 abrogates synaptic-vesicle priming in Caenorhabditis elegans neuromuscular junctions. These results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Structure, Tertiary
  • Rats
  • SNARE Proteins / metabolism
  • Synaptic Vesicles / metabolism*
  • Syntaxin 1 / metabolism*


  • Nerve Tissue Proteins
  • SNARE Proteins
  • Syntaxin 1
  • Unc13a protein, rat

Associated data

  • PDB/4Y21