CALCIUM-DEPENDENT REGULATION OF VOLTAGE-GATED CALCIUM CHANNELS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 电压门控钙通道（CaVs）是一种多亚基膜蛋白，在去极化时允许细胞外钙离子流入细胞质。 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和基因转录。 两个钙依赖性反馈过程调节其活性：钙依赖性失活（CDI）和钙依赖性易化（CDF）。这两个过程都是由钙调素（CaM）结合跨膜亚基调节。 此外，几种钙结合蛋白可以逆转CaM的作用。 在这里，我们希望对来自各种类型CaV的不同钙结合蛋白及其相互作用域之间的复合物的晶体进行衍射实验。 由此产生的结构将提供有价值的洞察这些复杂的蛋白质是如何调节钙，并给出了不同的CaV家族之间的功能差异的结构基础。

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.