Structure and Function of Copper Trafficking Proteins

该领域研究的广泛目标是开发一种完整的机械描述 细胞内铜的传递所涉及的蛋白质、调控过程和机制。 在过去的十年里，令人振奋的发展导致了对 铜的动态平衡及其重要性、毒性和在代谢中的关键作用。独一无二的氧化还原 铜的特性使其成为一系列关键酶的基本辅因子。虽然 这些酶很容易被识别(细胞色素c氧化酶、超氧化物歧化酶、多巴胺羟基酶 等)目前尚不清楚铜是如何通过体内、跨 膜，结合到酶中，回收和过量排泄。更不用说了解了 关于这些过程在正常和疾病状态下的机制。很明显，服务器 功能障碍是由铜代谢缺陷引起的，在某些人类基因中遇到 像Jvlenkes和Wilsons这样的疾病。利用简单、高度个性化的 Enteroccus hirae细菌系统，以前对铜的理解做出了贡献 将研究新陈代谢、关键的机制和调节问题。具体目标是： 1)表征铜从进口蛋白质到细胞内运输的假定转移 蛋白 2)评估运输蛋白中金属配体在吸引和捐献铜离子方面的作用 3)在分子水平上定义调节分子的金属传感机制。 实现这些目标将进一步促进对机制和-- 对铜进口和蜂窝分销流程的监管。

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.