Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and Exocytosis | Zendy

Hao Zhou | Zendy; Ziqing Wei | Zendy; Shen Wang | Zendy; Deqiang Yao | Zendy; Rongguang Zhang | Zendy; Cong Ma | Zendy

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Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and Exocytosis

Author(s) -

Hao Zhou,

Ziqing Wei,

Shen Wang,

Deqiang Yao,

Rongguang Zhang,

Cong Ma

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.02.064

Subject(s) - snare complex , munc 18 , exocytosis , microbiology and biotechnology , syntaxin , stx1a , secretion , chemistry , activator (genetics) , vesicular transport proteins , vesicle , biology , synaptic vesicle , endosome , biochemistry , receptor , membrane , vacuolar protein sorting , intracellular

Exocytosis of synaptic vesicles and dense-core vesicles requires both the Munc13 and CAPS (Ca 2+ -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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