Protein kinase C regulatory domain surrogate peptides: Effects of metal ions on folding, phorbol ester-binding, and selectivity

Abstract

The effects of zine and other metal ions on the folding and phorbol ester-binding of protein kinase C (PKC) surrogates have been investigated using the second cysteine-rich domain model peptides of rat PKCγ and mouse PKCη (γ-CRD2 and η-CRD2). The results clearly show that zinc plays an important role in the folding and phorbol ester-binding of these PKC surrogates. In addition, while treatment of these surrogates with various divalent first row transition metal ions other than zinc resulted in binding at background levels, treatment with copper, silver, gold, or mercury completely abolished binding. It is especially noteworthy that cadmium treated η-CRD2 showed a high level of binding while similarly treated γ-CRD2 exhibited no binding. These results suggest that recent reports on the inhibition of conventional PKC by heavy metal ions could be explained by their effects on the folding and binding of the CRD subunits.