title: NADP regulates the yeast GAL induction system.
abstract: Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UAS(GAL)); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key role in the initial induction event.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY11724, USA.
authors.forename: P Rajesh
authors.initials: PR
authors.lastname: Kumar
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.forename: Rolf
authors.initials: R
authors.lastname: Sternglanz
authors.forename: Stephen Albert
authors.initials: SA
authors.lastname: Johnston
authors.forename: Leemor
authors.initials: L
authors.lastname: Joshua-Tor
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins; D019281:Dimerization; D005686:Galactokinase / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008958:Models, Molecular; D009249:NADP / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C055002:GAL80 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D009249:NADP; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase; D005690:Galactose