We report spectroscopic studies that characterize the copper-binding properties of several synthetic zinc finger (ZF) peptides and the BIR2 domain of the X-linked Inhibitor of Apoptosis Protein (XIAP) that has recently been implicated in copper homeostasis. Cu(I) binds to the ZF peptides in both the apo- and metal-substituted forms, and the copper-binding stoichiometry is dependent on the number of cysteine residues at the metal binding site. Circular dichroism studies show that the conformations of the copper-bound complexes differ substantially from the Zn(II)-species, implying that copper-substituted zinc fingers are likely to be non-functional. The BIR2 domain of XIAP also exhibits a strong affinity for Cu(I). However, the high affinity binding site is mediated by one or more surface cysteine residues, and is likely distinct from the zinc-binding site. Mutagenesis-based experiments aimed at identifying the relevant copper-binding residues will be presented.

Copper(I) interactions with zinc finger domains

245th National Meeting (2013)

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