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Updated: Jan 27, 2026

Analysis of SNARE-mediated Membrane Fusion Using an Enzymatic Cell Fusion Assay
Published on: October 19, 2012
Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and
Hao Zhou1, Ziqing Wei1, Shen Wang1
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, China.
Abstract:
Exocytosis of synaptic vesicles and dense-core vesicles requires both the Munc13 and CAPS (Ca2+-dependent activator proteins for secretion) proteins. CAPS contains a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-binding region (called the DAMH domain), which has been found to be essential for SNARE-mediated exocytosis. Here we report a crystal structure of the CAPS-1 DAMH domain at 2.9-Å resolution and reveal a dual role of CAPS-1 in SNARE complex formation. CAPS-1 plays an inhibitory role dependent on binding of the DAMH domain to the MUN domain of Munc13-1, which hinders the ability of Munc13 to catalyze opening of syntaxin-1, inhibiting SNARE complex formation, and a chaperone role dependent on interaction of the DAMH domain with the syntaxin-1/SNAP-25 complex, which stabilizes the open conformation of Syx1, facilitating SNARE complex formation. Our results suggest that CAPS-1 facilitates SNARE complex formation via the DAMH domain in a manner dependent on sequential and cooperative interaction with Munc13-1 and SNARE proteins.
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