The Gal3p transducer of the GAL regulon interacts with the Gal80p repressor in its ligand-induced closed conformation

  1. Leemor Joshua-Tor1,2,3
  1. 1Keck Structural Biology Laboratory,
  2. 2Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

    Abstract

    A wealth of genetic information and some biochemical analysis have made the GAL regulon of the yeast Saccharomyces cerevisiae a classic model system for studying transcriptional activation in eukaryotes. Galactose induces this transcriptional switch, which is regulated by three proteins: the transcriptional activator Gal4p, bound to DNA; the repressor Gal80p; and the transducer Gal3p. We showed previously that NADP appears to act as a trigger to kick the repressor off the activator. Sustained activation involves a complex of the transducer Gal3p and Gal80p mediated by galactose and ATP. We solved the crystal structure of the complex of Gal3p–Gal80p with α-D-galactose and ATP to 2.1 Å resolution. The interaction between the proteins occurs only when Gal3p is in a “closed” state induced by ligand binding. The structure of the complex provides a rationale for the phenotypes of several well-known Gal80p and Gal3p mutants as well as the lack of galactokinase activity of Gal3p.

    Keywords

    Footnotes

    • Received November 4, 2011.
    • Accepted December 20, 2011.
    | Table of Contents

    Life Science Alliance