STRUCTURAL STUDIES OF MITOCHONDRIAL MEMBRANE PROTEINS AND CA-DEPENDENT REGULATIO

线粒体膜蛋白的结构研究和 CA 依赖性调节

• 批准号: 8362204
• 负责人: Eun-Young Kim
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362204
• 关键词: Aging; Binding; Calcium; Calcium Channel; Calcium Signaling; Calmodulin; Cell Death; Cells; Complex; Energy Metabolism; Funding; Grant; Human; Length; Light; Membrane; Mitochondria; Mitochondrial Membrane Protein; Mitochondrial Proteins; National Center for Research Resources; Play; Principal Investigator; Radiation; Regulation; Research; Research Infrastructure; Resources; Role; Source; Structure; United States National Institutes of Health; base; cost; macromolecule; research study; structural biology; voltage

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. (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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 (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。