Cadmium and lead interactions with transcription factor IIIA from Xenopus laevis: a model for zinc finger protein reactions with toxic metal ions and metallothionein

摘要

Zinc finger proteins comprise the largest class of eukaryotic transcription factors. The metal binding sites in these proteins have been proposed as plausible targets for exchange reactions between zinc and toxic metal ions that lead to the alteration of function of the proteins in gene transcription. According to the present work, both Cd²⁺ and Pb²⁺ displace Zn²⁺ from transcription factor IIIA (TFIIIA). Neither product binds to the internal control region (ICR) of the 5 S rRNA gene, the normal binding site for Zn-TFIIIA. Furthermore, the adduct of Zn-TFIIIA with ICR is also reactive with Cd²⁺ and Pb²⁺, leading to the dissociation of the DNA–protein complex. Cd-TFIIIA reacts with apometallothionein (apoMT) to form Cd-MT and apoTFIIIA. Similarly, Cd²⁺ and Zn²⁺ can be exchanged in the reaction of Cd-TFIIIA with Zn-MT. Zn-finger 3 of TFIIIA has also been examined to compare the reactivity of a single finger motif with fingers in the holoprotein. Zn-finger 3 reacts with much faster kinetics than the holoprotein.