Biophysical and biochemical studies of the mitochondrial uncoupling proteins

膜蛋白与细胞膜结合或与细胞膜相互作用。这些蛋白质负责多种生物功能，对维持生物体的生命至关重要，例如离子和营养物质在细胞膜上的运输以及通过促进电化学信号的传递在细胞之间的通信。在分子水平上了解这些功能的细节将大大提高对生命过程的洞察力，并有效地促进人类健康研究的几个领域。线粒体解偶联蛋白（UCPs）是本研究项目的重点。这些有趣的蛋白质位于某些动物和植物组织的线粒体内膜中，并将细胞中的呼吸与ATP合成分离。只有有限的信息已被记录在膜ucp的结构。除了其中一种蛋白质UCP1在调节幼龄哺乳动物体内温度方面的作用已得到证实外，其他ucp的详细生理作用尚不清楚。UCPs可能在氧化应激、脂质过氧化、糖尿病、发烧、炎症过程和神经系统保护中发挥作用。因此，详细研究ucp及其多样且明显不相关的生理作用，对于理解哺乳动物中参与重要生化过程调节的某些细胞系统的分子生物学具有重要意义。拟开展的研究项目将重点探索解偶联蛋白的膜结构、它们与膜的相互作用和在膜上的折叠，以及作为它们主要生物学功能的离子转运机制的细节。本研究计划是一个具有独创性的跨学科研究项目，将结构分析的光谱方法与合成、电生理、热化学和分子建模技术相结合，探索解偶联蛋白结构-功能关系的生物物理基础。

Membrane proteins are incorporated in and/or interact with the cell membranes.  These proteins are responsible for a variety of biological functions crucial for the maintenance of life in living organisms, such as transport of ions and nutrients across cell membranes and communication in between cells through facilitating the transfer of electrochemical signals.  Understanding the details of these functions at the molecular level will significantly improve the insight into the life processes and effectively contribute to several areas of human health research.  Mitochondrial uncoupling proteins (UCPs) are the focus of this research program. These intriguing proteins are located in the inner membranes of the mitochondria of certain animal and plant tissues, and uncouple the respiration from the ATP synthesis in cells. Only limited information has been documented on the structures of UCPs in membranes.  Apart from the well-established role of one of these proteins, UCP1, in regulating the temperature in the body of young mammals, the detailed physiological roles of other UCPs are not clearly understood. Possible roles of UCPs in response to oxidative stress, lipid peroxidation, diabetes, fever, inflammatory processes and nervous system protection have been suggested. Consequently, detailed studies of UCPs and their diverse and apparently unrelated physiological roles is significant in understanding the molecular biology of certain cellular systems that are involved in regulation of vital biochemical processes in mammals.   The proposed research program will focus on exploring the membrane structure of the uncoupling proteins, their interaction with and folding in membranes, and the details of the ion transport mechanism as their major biological function.  The proposed research program is original and interdisciplinary, and combines spectroscopic methods of structural analysis with synthetic, electrophysiological, thermochemical and molecular modeling techniques in an integrated study to explore the biophysical basis of the structure-function relationships in the uncoupling proteins.