Disruption of the zinc finger domain: A common target that underlies many of the effects of lead

The health risks associated with exposure to heavy metals such as lead (Pb) remain a major public health concern. The zinc finger is a major structura l motif involved in protein-nucleic acid interactions and is present in the largest superfamily of transcription factors. Zinc (Zn) ions coordinate th is finger-like structure through bonds created with cysteine and histidine residues. Little information exists on the effects of heavy metals on prote ins that contain structural repeats of this kind. Studies by us in the nerv ous system have shown that factors containing such motifs could be potentia l targets for perturbation by Pb. We have observed that metals such as Pb i nterfered with the DNA-binding properties of Sp1 and Egr-1, both in vivo an d in vitro. Pb could also directly interfere with the DNA-binding of a reco mbinant human Sp1 protein. More recently, the effects of Pb on the DNA-bind ing of the zinc finger protein transcription factor IIIA (TFIIIA) have been demonstrated. Analysis on the effects of Pb on Sp? revealed that alteratio ns in its DNA-binding were commensurate with changes in the expression of i ts target genes. The action of Pb on Sp1, Egr-1, and TFIIIA suggests that i t can also target other cellular proteins that contain the zinc finger moti f and reveals this protein domain asa potential mediator for Pb-induced alt erations in protein function. Thus by specifically targeting zinc finger pr oteins (ZFP) Pb is able to produce multiple responses through its action on a common site that is present in enzymes, channels and receptors. (C) 2000 Inter Press, Inc.