PROTEIN-KINASE-C REGULATORY DOMAIN SURROGATE PEPTIDES - EFFECTS OF METAL-IONS ON FOLDING, PHORBOL ESTER-BINDING, AND SELECTIVITY

The effects of zinc and other metal ions on the folding and phorbol es ter-binding of protein kinase C (PKC) surrogates have been investigate d using the second cysteine-rich domain model peptides of rat PKC gamm a and mouse PKC eta (gamma-CRD2 and eta-CRD2). The results clearly sho w that zinc plays an important role in the folding and phorbol eater-b inding 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 co pper, silver, gold, or mercury completely abolished binding. It is esp ecially noteworthy that cadmium treated eta-CRD2 showed a high level o f binding while similarly treated gamma-CRD2 exhibited no binding. The se results suggest that recent reports on the inhibition of convention al PKC by heavy metal ions could be explained by their effects on the folding and binding of the CRD subunits. (C) 1997 Elsevier Science Ltd .