STRUCTURAL STUDIES OF MITOCHONDRIAL MEMBRANE PROTEINS AND CA-DEPENDENT REGULATIO

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。 (1)线粒体在能量代谢、钙信号、衰老和细胞死亡中起中心作用。尽管它们很重要，但到目前为止，只有少数线粒体膜蛋白的结构被解决。我们结晶了一种人类线粒体蛋白，并希望进行衍射实验来解决其结构问题。由此产生的结构将阐明这些线粒体膜蛋白是如何发挥其功能的。 (2)电压门控钙通道(CAVs)是膜去极化时控制钙离子进入细胞内的多亚单位大分子。钙调蛋白(CaM)通过与Cav？1C末端结合，在CAV的钙依赖调节中发挥重要作用。虽然已经对Cav-CaM相互作用进行了大量的功能研究，但CaV对CaM调控的结构细节仍然不清楚。为了阐明Cav调控的结构基础，我们在Cav？1C末端不同长度的CaM结合基序的复合体中制备了不同CaM状态的晶体。

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. (1) Mitochondria play a central in role energy metabolism, calcium signaling, aging, and cell death. Despite their importance, only few structures of mitochondrial membrane protein have been solved so far. We crystallized one of the human mitochondrial proteins and wish to perform diffraction experiments to solve its structure. The resulting structure will shed a light on how these mitochondrial membrane proteins exert their functions. (2) Voltage-gated calcium channels (Cavs) are multi-subunit macromolecules that control calcium entry into cells upon membrane depolarization. Calmodulin (CaM) plays a critical role in calcium-dependent modulation of CaVs through association with the Cav ?1 C-terminus. Although a multitude of functional studies of the CaV-CaM interaction have been carried out, the structural details of CaM modulation of CaVs remain unclear. To elucidate the structural basis of CaV regulation, we have prepared crystals of different CaM states in complexes with different lengths of CaM binding motifs from CaV ?1 C-terminus.