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Structure and Function of Copper Trafficking Proteins

铜运输蛋白的结构和功能

基本信息

批准号：
7673016
负责人：
CHARLES T DAMERON
金额：
$ 7.5万
依托单位：
SAINT FRANCIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2010-04-30
项目状态：
已结题

项目摘要

The broad goal of the research in the area is to develop a complete mechanistic description of the proteins, regulatory processes and mechanisms involved in the intracellular routing of copper. Exciting developments over the past decade have lead to an increase in the understanding of copper homeostasis, its essentiality, toxicity and pivotal role in metabolism. The unique redox properties of copper make it an essential cofactor for a wide range of critical enzymes. Although these enzymes are readily identified (cytochrome c oxidase, superoxide dismutase, dopamine phydroxylase etc.) it is still not understood how copper is transported through the body, across membranes, incorporated into enzymes, recycled and excess excreted. Still less is understood about the mechanisms of these processes in normal and diseased states. It is clear that sever dysfunctions result from defects in copper metabolism, encountered in some human genetic diseases likeJvlenkes and Wilsons. Utilizing the features of the simple, highly characterized Enteroccus hirae bacterial system, that contributed previously to the understanding of copper metabolism, key mechanistic and regulatory questions will be investigated. The specific aims are: 1) characterize the putative transfer of copper from an import protein to a intracellular transport protein 2) evaluate the role of the metal ligands in a transport protein to attract and donate copper ions 3) define, at a molecular level, the metal sensing mechanism of a regulatory molecule. Accomplishment of these goals will further advance the understanding of the mechanisms and the - regulation of the copper import and cellular distribution processes.

该领域研究的主要目标是开发一个完整的机械描述，蛋白质，调节过程和机制参与细胞内的铜路由。过去十年来令人兴奋的事态发展使人们更加了解铜的体内平衡，它的必要性，毒性和代谢中的关键作用。独特的氧化还原铜的特性使其成为广泛的关键酶的必需辅因子。虽然这些酶很容易鉴定（细胞色素C氧化酶、超氧化物歧化酶、多巴胺羟化酶等等）。目前还不清楚铜是如何通过身体，膜，纳入酶，回收和多余的排泄。更不被理解关于这些过程在正常和疾病状态下的机制。很明显，功能障碍是由于铜代谢缺陷引起的，在一些人类遗传性疾病中，像Jvlenkes和威尔逊病。利用简单、高度个性化的特点，肠球菌细菌系统，这有助于以前的理解铜代谢，关键机制和监管问题将进行调查。具体目标是： 1)表征铜从输入蛋白到细胞内转运的假定转移蛋白 2)评估转运蛋白中金属配体吸引和提供铜离子的作用 3)在分子水平上定义调节分子的金属传感机制。这些目标的实现将进一步促进对机制的理解，铜进口和蜂窝分配过程的监管。