XAS STUDIES ON COPPER TRANSPORTERS AND CHAPERONES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。铜稳态对健康的细胞代谢至关重要。铜转运和调控的异常与许多疾病有关，包括Wilson和Menkes病，FALS (Lou Gehrig's disease)，以及最近的朊病毒疾病，如痒病和疯牛病。XAS将用于探测铜转运体p型atp酶Menkes蛋白（MNKP）和Wilsons蛋白（WNDp）及其伴侣hai的金属中心结构。多元素方法将用于研究蛋白质与其伴侣之间的相互作用，通过用Ag(I)或Hg（II）取代hai，并与Cu(l)结合的MNKP或WNDp形成复合物。将对SOD及其伴侣蛋白CCSP的相互作用进行类似的研究。该计划的目标是更好地了解金属蛋白伴侣系统中金属结合和转运的机制。Cu(I), Ag(I)和Hg(I)对大多数其他形式的光谱的不可见性强调了XAS在这一重要领域的独特作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Copper homeostasis is essential to healthy cellular metabolism. Abnormalities in copper transport and regulation have been linked to a number of diseases including Wilson and Menkes diseases, FALS (Lou Gehrig's disease), and more recently Prion diseases such as scrapie and BSE. XAS will be used to probe the structure of the metal centers in the copper transporter P-type ATPases Menkes Protein (MNKP) and Wilsons Protein (WNDp), and their chaperone HAH I. A multielement approach will be used to study the interaction between the proteins and their chaperone, via substitution of the HAH I with Ag(I) or Hg(II), and complex formation with the Cu(l)-bound MNKP or WNDP. Similar studies will be carried out on SOD and its interaction with its chaperone CCSP. The goal of the program is to obtain a better understanding of the mechanisms of metal binding and translocation in the metalloproteinchaperone systems. The invisibility of the Cu(I), Ag(I) and Hg(I) to most other forms of spectroscopy emphasizes the unique role of XAS in this important field.