STRUCTURE OF THE DNA-BINDING DOMAIN OF ZINC GAL4

THE yeast transcriptional activator GAL4 binds co-operatively to four related 17-base-pair sequences within an upstream activating sequence (UAS(G)) to activate transcription of the GAL1 and GAL10 genes 1. It belongs to a class of gene regulatory proteins which all contain a highly conserved cysteine-rich region within their DNA-binding domains 2,3. This region binds zinc 4-7 and it has been proposed that the cysteine residues coordinate the zinc, creating a structure analogous to one of the 'zinc fingers' of the transcription factor TFIIIA (ref. 8). Using H-1-Cd-113 two-dimensional nuclear magnetic resonance spectra of the cadmium form of the domain, we previously showed that the protein contains a Cd2Cys6 cluster where cysteines 11 and 28 act as bridging ligands 9. A similar study of a fragment of GAL4 has recently been published 10. We report here the solution structure of the DNA binding domain of GAL4; two helix-turn-strand motifs pack around a Zn2Cys6 cluster in a novel pseudo-symmetrical arrangement. The results show that the GAL4 zinc-binding domain differs significantly from both the TFIIIA-type zinc finger 11 and the steroid hormone receptor DNA-binding domains 12.