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NIH Molecular Toxicology Postdoctoral Fellow, Northwestern
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Our laboratory is interested in the structure, function, and biochemistry of metalloproteins. Recently a new class of proteins, termed metallochaperones, were discovered that deliver copper ions within the cytosol to specific intracellular targets. In humans, these targets include the Wilsons and Menkes disease proteins, copper-transporting ATPases. Mutations in these proteins lead to disorders of copper metabolism. In both the metallochaperones and the metal-binding ATPase domains the copper ion is housed in a surface-exposed loop (Figure) to facilitate rapid transfer with partner. We are interested in the mechanisms by which these metal ion delivery pathways are shortcircuited, either via mutations in the ATPase domains or by the acquisition of non-native metal ions. This is a potential pathway for the acquisition of toxic metal ions such as Hg(II), and Cd(II). |
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Figure. Ribbon structure of metal-binding domain 1 of Ccc2a, a P-type ATPase, with bound copper. |