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Munc18-1 induces conformational changes of syntaxin-1 in multiple intermediates for SNARE assembly.
Sanghwa Lee1, Jonghyeok Shin2,3, Younghun Jung2
1Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea. sanglee@gist.ac.kr.
Scientific Reports
|July 17, 2020
Summary
Munc18-1 acts as a gatekeeper in neuronal exocytosis by locking syntaxin-1, a key SNARE protein, in a closed conformation. This regulates the formation of essential SNARE complexes for membrane fusion.
Area of Science:
- Molecular Biology
- Neuroscience
- Biochemistry
Background:
- Neuronal exocytosis relies on SNARE complex assembly for membrane fusion.
- The SM protein Munc18-1 is crucial for precise SNARE assembly, but its mechanism is unclear.
Purpose of the Study:
- To investigate the conformational dynamics of SNARE/Munc18-1 complexes during SNARE assembly.
- To elucidate the role of Munc18-1 in regulating SNARE complex formation.
Main Methods:
- Single-molecule Förster Resonance Energy Transfer (smFRET) assays.
- Nanodisc membrane reconstitution system.
- Kinetic analysis of protein conformational transitions.
Main Results:
- Munc18-1 induces a closed conformation in syntaxin-1, both alone and within the t-SNARE complex.
- Munc18-1 acts as a gatekeeper, controlling binary and ternary SNARE complex formation.
- The ternary SNARE complex favors an open syntaxin-1 conformation more than the binary complex.
Conclusions:
- Munc18-1's gatekeeper function is essential for regulating SNARE assembly in neuronal exocytosis.
- Understanding these conformational dynamics provides insights into the precise control of membrane fusion.
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