Biochemical regulation of mitochondrial uncoupling protein 3

描述（由申请人提供）：解偶联蛋白（UCPs）是线粒体！内膜阴离子载体蛋白在物种间具有良好的保守性。UCPs耗散了电子传递链通过初级底物乙酰辅酶a代谢而产生的质子梯度。ucp具有多种功能，包括非寒颤产热、消耗多余底物和减少活性氧。尽管这些蛋白具有多种功能，但还没有发现其他蛋白与任何UCP直接相互作用。最近的酵母- 2杂交实验结果表明，蛋白2,4,3,5二烯酰辅酶a异构酶（DDI）结合解偶联蛋白3 （UCPS）的亲水性环1、2和4。当这些蛋白在培养的哺乳动物细胞中过表达时，通过共免疫沉淀也观察到这种相互作用。DDI蛋白是β氧化途径的辅助蛋白，它将不饱和脂肪酸的奇数双键移动到偶数位置，以便为催化生成乙酰辅酶- a做准备。该项目将利用生物化学、细胞生物学和分子生物学方法探索这种蛋白质相互作用的本质。更具体地说，我们将绘制UCP3:DDI相互作用结构域，并确定蛋白质影响其他蛋白质功能的程度。这项研究与公众健康的相关性：身体使用能量和分解脂肪的方式异常在许多疾病中起着重要作用。这项研究将为代谢紊乱（如糖尿病和肥胖）之间的联系提供新的见解，并可能最终为患者带来更先进的治疗选择。

DESCRIPTION (provided by applicant): Uncoupling proteins (UCPs) are mitochondria! inner membrane anion carrier proteins that are well conserved across species. UCPs dissipate the proton gradient that is generated by the electron transport chain through the metabolism of the primary substrate acetyl Co-A. UCPs have diverse functions including non-shivering thermogenesis, expenditure of excess substrates, and reduction of reactive oxygen species. Despite the various functions performed by these proteins, no other protein has been found to directly interact with any UCP. Recent results of a yeast-two hybrid experiment indicate that the protein delta 2,4, delta 3,5 dienoyl-CoA isomerase (DDI) binds hydrophilic loops 1, 2, and 4 of uncoupling protein 3 (UCPS). This interaction was also observed via co-immunoprecipitation when these proteins were overexpressed in cultured mammalian cells. The protein DDI is an auxiliary protein of the beta oxidation pathway that moves odd-numbered double bonds of unsaturated fatty acids to even-numbered positions in order to prepare them for catalysis into acetyl Co-A. This project will explore the nature of this protein interaction using biochemical, cell biological, and molecular biology methodologies. More specifically, we will map the UCP3:DDI interacting domains and ascertain the extent to which the proteins influence the functions of the other. Relevance of this research to public health: Abnormalities in how the body uses energy and breaks down fat play an important part in numerous diseases. This research will provide new insight on the link between metabolic disorders, such as diabetes and obesity, and may ultimately lead to more advanced treatment options for patients.