Zinc finger proteins: what we know and what we would like to know

The molecular description of diverse nucleic acid binding proteins has led to the definition of structurally related families of such polypeptides. They often carry multiple modular functional domains, and one conserved motif responsible for nucleic acid binding is the zinc finger repeat. It has originally been discovered in TFIIIA, a 5S gene specific transcription factor from Xenopus. This protein contains nine tandem repeats of a sequence element referred to as the C2H 2 zinc finger since it contains highly conserved pairs of cysteine and histidine residues (Miller et al., 1985; Brown et al., 1985), which fold each of these sequences about a zinc atom (Diakun et al., 1986). Following its discovery in TFIIIA, variants of the zinc finger motif have been detected in many other, often regulatory proteins. It should be pointed out that the term 'zinc finger' has been applied to several other structures such as the cysteine rich DNA binding domain of ligand dependent nuclear receptors (Evans, 1988; Green and Chambon, 1988; Beato, 1989) or a group of retroviral RNA binding proteins (Katz and Jentoft, 1989)'. Here, we will focus our discussion on the C2H 2 class of zinc finger proteins (ZFPs), of which TFIIIA is a prototype.