Cu (I) exhibits high affinity for thiolate ligands, suggesting that thiol-rich zinc or iron-binding sites may be subject to disruption during copper stress conditions. Zinc fingers constitute a large class of metalloproteins that employ a combination of cysteine and histidine residues that bind zinc as a structural element. Despite the shared preference of both copper and zinc for thiolate coordination, the susceptibility of zinc finger domains toward copper substitution has not been well-characterized. Herein we report spectroscopic studies that characterize the copper-binding properties of the C-terminal zinc finger domain of the HIV-1 nucleocapsid protein (NCp7). Cu (I) binds to both the apo- and cobalt-substituted peptides with a 2:1 metal:peptide stoichiometry, implying that Cu (I) can disrupt the structure of the properly folded peptide. Fluorescence studies of the Zn (II)-NCp7 complex indicate that Cu (I) also effectively competes with zinc at the metal binding site, despite the high affinity of zinc for the CCHC binding motif. The implications of copper substitution at zinc-binding domains will be discussed in the context of both copper  toxicity and copper sensing and regulation.

Spectroscopic characterization of copper binding to zinc finger domains

243rd National Meeting (2012)

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