title: Genesis of eukaryotic transcriptional activator and repressor proteins by splitting a multidomain anabolic enzyme.
abstract: The genes necessary for the correctly regulated catabolism of quinate in Aspergillus nidulans and Neurospora crassa are controlled at the level of transcription by a DNA-binding activator protein and a repressor protein that directly interact with one another. The repressor protein is homologous throughout its length with the three C-terminal domains of a pentafunctional enzyme catalysing five consecutive steps in the related anabolic shikimate pathway. We now report that the activator protein is homologous to the two N-terminal domains of the same pentafunctional enzyme and that this proposed structural similarity suggests a molecular mechanism by which the repressor recognises the activator protein. We believe that this is the first report of the genesis of a pair of interacting eukaryotic regulatory proteins by the splitting of a multidomain anabolic enzyme. The recruitment of preformed enzymatically active domains to a regulatory role may represent a general mechanism for the evolution of pathway-specific regulator proteins in dispensable pathways.
authors.affiliation: Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Hawkins
authors.forename: H K
authors.initials: HK
authors.lastname: Lamb
authors.forename: J D
authors.initials: JD
authors.lastname: Moore
authors.forename: C F
authors.initials: CF
authors.lastname: Roberts
mesh_terms: D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D008190:Lyases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009492:Neurospora crassa / Q000235:genetics; D019761:Phosphorus-Oxygen Lyases; D011801:Quinic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014166:Transferases / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D011801:Quinic Acid; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D008190:Lyases; D006836:Hydro-Lyases; C020000:3-dehydroquinate dehydratase; C020001:3-dehydroquinate synthetase; D019761:Phosphorus-Oxygen Lyases