STRUCTURAL STUDIES OF MITOCHONDRIAL MEMBRANE PROTEINS AND CA-DEPENDENT REGULATIO

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 (1)线粒体在能量代谢、钙信号传导、衰老和细胞死亡中起核心作用。 尽管它们的重要性，只有少数线粒体膜蛋白的结构已被解决到目前为止。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。由此产生的结构将揭示这些线粒体膜蛋白如何发挥其功能。(2)电压门控钙通道（Cavs）是一种多亚基大分子，在膜去极化时控制钙进入细胞。钙调素（CaM）通过与CaV C-末端结合在CaV的钙依赖性调节中起关键作用。 虽然大量的功能研究的CaV-CaM相互作用已经进行，CaV的CaM调制的结构细节仍然不清楚。 为了阐明CaV调控的结构基础，我们制备了不同CaM状态的晶体，这些晶体在CaV C-末端具有不同长度的CaM结合基序。

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 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 C-terminus.