XAS STUDIES ON COPPER TRANSPORTERS AND CHAPERONES

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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.