Crystal Structure of the C-Terminal WD40 Repeat Domain of the Human Groucho/TLE1 Transcriptional Corepressor
Copyright policy )Crystal Structure of the C-Terminal WD40 Repeat Domain of the Human Groucho/TLE1 Transcriptional Corepressor
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.
- Montreal Neurological Institute and Hospital Canada
- Institute of Cancer Research United Kingdom
Amino Acid Motifs, Molecular Sequence Data, Crystallography, X-Ray, chromatin remodeling, protein-protein interaction, β propeller, Structural Biology, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Amino Acid Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Molecular Biology, transcription factor, Nuclear Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, Repressor Proteins, Amino Acid Substitution, developmental regulation, Mutation, mutation, Co-Repressor Proteins, Sequence Alignment, Transcription Factors
Amino Acid Motifs, Molecular Sequence Data, Crystallography, X-Ray, chromatin remodeling, protein-protein interaction, β propeller, Structural Biology, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Amino Acid Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Molecular Biology, transcription factor, Nuclear Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, Repressor Proteins, Amino Acid Substitution, developmental regulation, Mutation, mutation, Co-Repressor Proteins, Sequence Alignment, Transcription Factors
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