title: Crystal structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 transcriptional corepressor.
abstract: Groucho (Gro)/TLE proteins are transcriptional corepressors that lack inherent DNA binding but interact with DNA-bound transcription factors and histones, and recruit histone deacetylases. Groucho-mediated repression is essential in embryonic development and involved in regulation of Wnt signaling in adult tissue. We have determined the 1.6 A crystal structure of a C-terminal fragment of human Groucho/TLE1, comprising part of the Ser/Pro-rich region and a seven-bladed beta propeller WD40 repeat domain, implicated in protein-protein interactions. The structure confirms the relationship to the yeast Tup1 corepressor, but reveals important structural differences specific to the metazoan system. Analysis of missense mutations in the C. elegans Groucho homolog UNC-37 identifies sites of interaction with repression effectors, and suggests an induced fit binding site for eh1 domains of Engrailed-type transcription factors.
authors.affiliation: Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB, London, United Kingdom.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Pickles
authors.forename: S Mark
authors.initials: SM
authors.lastname: Roe
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Hemingway
authors.forename: Stefano
authors.initials: S
authors.lastname: Stifani
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Pearl
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D056970:Co-Repressor Proteins; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C499043:TLE1 protein, human; C091023:gro protein, Drosophila; C106184:unc-37 protein, C elegans