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Updated: May 21, 2026
06:45
In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve Terminal
Published on: January 14, 2018
Low-resolution solution structures of Munc18:Syntaxin protein complexes indicate an open binding mode driven by the
Michelle P Christie1, Andrew E Whitten, Gordon J King
1Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia.
Summary
The Munc18 protein interacts with Syntaxin proteins to regulate vesicle fusion. Neuronal Munc18-1:Syntaxin1a can adopt two binding modes, while adipocyte Munc18c:Syntaxin4 uses only one, depending on the Syntaxin N-peptide presence.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Vesicle fusion is crucial for neuronal communication and glucose uptake, mediated by SNARE proteins and Munc18.
- Munc18 proteins bind Syntaxin proteins, but the structural basis and regulation of these interactions are not fully understood.
Purpose of the Study:
- To investigate the binding modes of neuronal Munc18-1:Syntaxin1a and adipocyte Munc18c:Syntaxin4 complexes.
- To determine the role of the Syntaxin N-peptide in regulating Munc18-Syntaxin complex formation and structure.
Main Methods:
- Solution scattering (SAXS/SANS) with contrast variation
- Cross-linking/mass spectrometry
- Crystal structure analysis
Main Results:
- Neuronal Munc18-1:Syntaxin1a binds in a closed inhibitory mode without the N-peptide and an open extended mode with the N-peptide.
- Adipocyte Munc18c:Syntaxin4 requires the N-peptide and adopts only the open binding mode.
- Structural data reveal distinct interactions in the open Munc18:Syntaxin binding mode compared to the closed mode.
Conclusions:
- The Syntaxin N-peptide dictates the binding mode of Munc18-Syntaxin complexes.
- Neuronal and adipocyte Munc18-Syntaxin interactions exhibit differential regulation by the N-peptide, impacting their distinct cellular functions.
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