6A68

the crystal structure of rat calcium-dependent activator protein for secretion (CAPS) DAMH domain

Summary for 6A68

• Entry DOI: 10.2210/pdb6a68/pdb
• Descriptor: Calcium-dependent secretion activator 1, POTASSIUM ION (3 entities in total)
• Functional Keywords: exocytosis dcv transition, exocytosis
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 1
• Total formula weight: 21601.77

Authors

Zhou, H.,Wei, Z.Q.,Yao, D.Q.,Zhang, R.G.,Ma, C. (deposition date: 2018-06-26, release date: 2019-03-13, Last modification date: 2024-10-23)

Primary citation

Zhou, H.,Wei, Z.,Wang, S.,Yao, D.,Zhang, R.,Ma, C.
Structural and Functional Analysis of the CAPS SNARE-Binding Domain Required for SNARE Complex Formation and Exocytosis.
Cell Rep, 26:3347-3359.e6, 2019

PubMed Abstract: Exocytosis of synaptic vesicles and dense-core vesicles requires both the Munc13 and CAPS (Ca-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.

PubMed: 30893606
DOI: 10.1016/j.celrep.2019.02.064

Experimental method

X-RAY DIFFRACTION (2.901 Å)