CALCIUM-DEPENDENT REGULATION OF VOLTAGE-GATED CALCIUM CHANNELS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 电压门控钙通道(CAVs)是一种多亚单位膜蛋白，在去极化时允许细胞外钙流入细胞质。它们控制神经递质和激素的分泌，肌肉收缩的启动，心脏细胞的起搏器活动，以及基因转录。两个钙依赖的反馈过程调节它们的活性：钙依赖失活(CDI)和钙依赖促进(CDF)。这两个过程都受钙调素(CaM)与跨膜亚单位结合的调节。此外，几种钙结合蛋白可以逆转CaM的作用。在这里，我们希望对来自不同类型CAV的不同钙结合蛋白及其相互作用结构域之间的复合物晶体进行衍射实验。由此得到的结构将为这些复杂蛋白如何受钙调控提供有价值的见解，并为不同CAV家族之间的功能差异提供结构基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Voltage-gated calcium channels (CaVs) are multisubunit membrane proteins that allow the influx of extracellular calcium into the cytoplasm upon depolarization. They control secretion of neurotransmitters and hormones, initiation of muscle contraction, the pacemaker activity of heart cells, and gene transcription. Two calcium-dependent feedback processes regulate their activity: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Both processes are regulated by calmodulin (CaM) binding to the transmembrane subunit. In addition, several calcium binding proteins can reverse the effect of CaM. Here, we wish to perform diffraction experiments on crystals of complexes between different calcium binding proteins and their interaction domains from various types of CaVs. The resulting structures will provide valuable insight into how these complex proteins are regulated by calcium, and give a structural basis for the functional differences between the different CaV families.