Ca²⁺-dependent activator proteins for secretion (CAPSs) are required for Ca²⁺-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 C₂ domain residing adjacent to the PH domain, but its function remains unclear. In this study, we solved the crystal structure of the CAPS-1 C₂PH module. The structure showed that the C₂ and PH tandem packs against one another mainly via hydrophobic residues. With this interaction, the C₂PH 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 C₂ domain. Disruption of either the tight interaction between the C₂ and PH domains or the PI(4,5)P2-binding sites on both domains significantly impairs CAPS-1 function in Ca²⁺-regulated exocytosis at the Caenorhabditis elegans neuromuscular junction (NMJ). These results suggest that the C₂ and PH domains constitute an effective unit to promote Ca²⁺-regulated exocytosis.

神经元和神经内分泌细胞中 Ca 2+ 调节的胞吐作用^需要Ca 2+ 依赖性分泌激活蛋白 (CAPS ) ^。CAPS 包含结合 PI(4,5)P2 膜的 pleckstrin 同源 (PH) 结构域。还有一个 C ₂结构域与 PH 结构域相邻，但其功能尚不清楚。_{在这项研究中，我们解决了 CAPS-1 C 2} PH 模块的晶体结构。该结构表明 C ₂和 PH 主要通过疏水残基相互串联。通过这种相互作用，与分离的 PH 结构域相比，C _{2 PH 模块与 PI(4,5)P2 膜的结合增强。}此外，我们在 C 上发现了一个新的 PI(4,5)P2 结合位点₂域。破坏 C ₂和 PH 结构域之间的紧密相互作用或两个结构域上的 PI(4,5)P2 结合位点会显着损害秀丽隐杆线虫神经肌肉接头(NMJ)中 Ca ²⁺调节的胞吐作用中的 CAPS-1 功能. 这些结果表明C _{2和PH 结构域构成了促进Ca} ²⁺调节的胞吐作用的有效单位。