Molecular recognition of transcriptional repressor motifs by the WD domain of the Groucho/TLE corepressor.

The Groucho (Gro)/TLE/Grg family of corepressors operates in many signaling pathways (including Notch and Wnt). Gro/TLE proteins recognize a wide range of transcriptional repressors by binding to divergent short peptide sequences, including a C-terminal WRPW/Y motif (Hairy/Hes/Runx) and internal eh1 motifs (FxIxxIL; Engrailed/Goosecoid/Pax/Nkx). Here, we identify several missense mutations in Drosophila Gro, which demonstrate peptide binding to the central pore of the WD (WD40) beta propeller domain in vitro and in vivo.

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.