2CE9

A WRPW peptide bound to the Groucho-TLE WD40 domain.

Summary for 2CE9

• Entry DOI: 10.2210/pdb2ce9/pdb
• Related: 1GXR 2CE8
• Descriptor: TRANSDUCIN-LIKE ENHANCER PROTEIN 1, WRPW PEPTIDE (3 entities in total)
• Functional Keywords: transcriptional co-repressor, wd40 domain, wnt signaling pathway, nuclear protein, phosphorylation, repressor, transcription, transcription regulation, wd repeat
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 6
• Total formula weight: 148965.75

Authors

Pickles, L.M.,Roe, S.M.,Pearl, L.H. (deposition date: 2006-02-03, release date: 2006-06-14, Last modification date: 2023-12-13)

Primary citation

Jennings, B.H.,Pickles, L.M.,Wainwright, S.M.,Roe, S.M.,Pearl, L.H.,Ish-Horowicz, D.
Molecular Recognition of Transcriptional Repressor Motifs by the Wd Domain of the Groucho/Tle Corepressor.
Mol.Cell, 22:645-, 2006

PubMed Abstract: 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. We define these interactions at the molecular level with crystal structures of the WD domain of human TLE1 bound to either WRPW or eh1 peptides. The two distinct peptide motifs adopt markedly different bound conformations but occupy overlapping sites across the central pore of the beta propeller. Our structural and functional analysis explains the rigid conservation of the WRPW motif, the sequence flexibility of eh1 motifs, and other aspects of repressor recognition by Gro in vivo.

PubMed: 16762837
DOI: 10.1016/J.MOLCEL.2006.04.024

Experimental method

X-RAY DIFFRACTION (2.12 Å)