Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex

Structure. 2008 Feb;16(2):308-20. doi: 10.1016/j.str.2007.12.010.

Abstract

Syntaxin/SNAP-25 interactions precede assembly of the ternary SNARE complex that is essential for neurotransmitter release. This binary complex has been difficult to characterize by bulk methods because of the prevalence of a 2:1 dead-end species. Here, using single-molecule fluorescence, we find the structure of the 1:1 syntaxin/SNAP-25 binary complex is variable, with states changing on the second timescale. One state corresponds to a parallel three-helix bundle, whereas other states show one of the SNAP-25 SNARE domains dissociated. Adding synaptobrevin suppresses the dissociated helix states. Remarkably, upon addition of complexin, Munc13, Munc18, or synaptotagmin, a similar effect is observed. Thus, the 1:1 binary complex is a dynamic acceptor for synaptobrevin binding, and accessory proteins stabilize this acceptor. In the cellular environment the binary complex is actively maintained in a configuration where it can rapidly interact with synaptobrevin, so formation is not likely a limiting step for neurotransmitter release.

Publication types

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

MeSH terms

  • Fluorescence Resonance Energy Transfer
  • Lipid Bilayers / metabolism
  • Protein Structure, Tertiary
  • Qa-SNARE Proteins / chemistry*
  • Qa-SNARE Proteins / metabolism
  • R-SNARE Proteins / metabolism*
  • SNARE Proteins / metabolism*
  • Synaptosomal-Associated Protein 25 / chemistry*
  • Synaptosomal-Associated Protein 25 / metabolism

Substances

  • Lipid Bilayers
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • SNARE Proteins
  • Synaptosomal-Associated Protein 25