The Interaction between an Acidic Transcriptional Activator and Its Inhibitor

Abstract

The GAL genes, which encode the enzymes required for nor- mal galactose metabolism in yeast, are transcriptionally regu- lated by three proteins: Gal4p, an activator; Gal80p, an inhibi- tor; and Gal3p, a galactose sensor. These proteins control the switch between inert and active gene expression. The transcrip- tional activation function of Gal4p is rendered inactive in the presence of Gal80p. Here we present the three-dimensional structure of a complex between the acidic activation domain of Gal4p and Gal80p. The transactivation domain initiates with an extended region of polypeptide chain followed by two turns of an amphipathic -helix. It fits into and across a deep cleft within theGal80pdimerwith the protein-protein interface defined pri- marily by hydrophobic interactions. A disordered loop in the apo-Gal80p structure (Asp-309 to Ser-316) becomes well-de- fined upon binding of the transactivation domain. This investi- gation provides anewmolecular scaffold for understanding pre- vious biochemical and genetic studies.