7VS3

The crystal structure of rat calcium-dependent activator protein for secretion (CAPS) C2PH

Summary for 7VS3

• Entry DOI: 10.2210/pdb7vs3/pdb
• Descriptor: Calcium-dependent secretion activator 1, SULFATE ION (3 entities in total)
• Functional Keywords: ca2+-dependent exocytosis; vesicle priming; munc13; caps; snare complex assembly, exocytosis
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 1
• Total formula weight: 27973.81

Authors

Zhou, H.,Wei, Z.Q.,Zhang, L.,Ren, Y.J.,Ma, C. (deposition date: 2021-10-25, release date: 2023-02-15, Last modification date: 2023-11-29)

Primary citation

Zhang, L.,Li, L.,Wei, Z.,Zhou, H.,Liu, H.,Wang, S.,Ren, Y.,Dai, T.,Wang, J.,Hu, Z.,Ma, C.
The C 2 and PH domains of CAPS constitute an effective PI(4,5)P2-binding unit essential for Ca 2+ -regulated exocytosis.
Structure, 31:424-, 2023

PubMed Abstract: Ca-dependent activator proteins for secretion (CAPSs) are required for Ca-regulated exocytosis in neurons and neuroendocrine cells. CAPSs contain a pleckstrin homology (PH) domain that binds PI(4,5)P2-membrane. There is also a C domain residing adjacent to the PH domain, but its function remains unclear. In this study, we solved the crystal structure of the CAPS-1 CPH module. The structure showed that the C and PH tandem packs against one another mainly via hydrophobic residues. With this interaction, the CPH module exhibited enhanced binding to PI(4,5)P2-membrane compared with the isolated PH domain. In addition, we identified a new PI(4,5)P2-binding site on the C domain. Disruption of either the tight interaction between the C and PH domains or the PI(4,5)P2-binding sites on both domains significantly impairs CAPS-1 function in Ca-regulated exocytosis at the Caenorhabditis elegans neuromuscular junction (NMJ). These results suggest that the C and PH domains constitute an effective unit to promote Ca-regulated exocytosis.

PubMed: 36863339
DOI: 10.1016/j.str.2023.02.004

Experimental method

X-RAY DIFFRACTION (2.595 Å)