PDBsum entry 2ce9

Transcription regulation

PDB id: 2ce9

Contents

Protein chains

337 a.a. *

Ligands

MET-TRP-ARG-PRO-TRP ×2

Waters ×861

* Residue conservation analysis

PDB id:

2ce9

Name:

Transcription regulation

Title:

A wrpw peptide bound to the groucho-tle wd40 domain.

Structure:

Transducin-like enhancer protein 1. Chain: a, b, c, d. Fragment: partial sp and whole wd40 domains, residues 443-770. Synonym: esg1, e(sp1) homolog. Engineered: yes. Wrpw peptide. Chain: x, y. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Organism_taxid: 9606

Biol. unit:

Trimer (from PDB file)

Resolution:

2.12Å R-factor: 0.181 R-free: 0.244

Authors:

L.M.Pickles,S.M.Roe,L.H.Pearl

Key ref:

B.H.Jennings et al. (2006). Molecular recognition of transcriptional repressor motifs by the WD domain of the Groucho/TLE corepressor. Mol Cell, 22, 645-655. PubMed id: 16762837 DOI: 10.1016/j.molcel.2006.04.024

Date:

03-Feb-06 Release date: 14-Jun-06

Protein chains

Q04724  (TLE1_HUMAN) -  Transducin-like enhancer protein 1 from Homo sapiens

Seq: 770 a.a.

Struc: 337 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1016/j.molcel.2006.04.024

Mol Cell 22:645-655 (2006)

PubMed id: 16762837

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

B.H.Jennings, L.M.Pickles, S.M.Wainwright, S.M.Roe, L.H.Pearl, D.Ish-Horowicz.

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.

Selected figure(s)

Figure 4.
Figure 4. Binding of the WRPW and eh1 Peptide Motifs to the TLE-WD Domain
(A) Backbone of the SMWRPW peptide (purple) from human Hes1 on TLE-WD (ribbons) showing that binding occurs across the pore.
(B) Close-up view of the WPRW core revealing its compact orientation.
(C) Detailed intermolecular interactions between the WRPW core and adjacent amino acids in the WD domain. L743, corresponding to the aminoacid mutated in MB31, is underlined.
(D) The eh1 peptide backbone (purple) from human Gsc on TLE-WD (ribbons) indicating the site of peptide binding and its α-helical structure.
(E) Close-up view of the eh1 core heptapeptide showing its elongated structure.
(F) Detailed intermolecular interactions between the core peptide and adjacent aminoacids in the WD domain showing that contacts are made to the similar amino acids as for WRPW (C).

Figure 5.
Figure 5. Common Conformational Features of Bound WRPW and eh1 Motifs
Superposition of the WRPW and eh1 peptides in their bound conformations, showing the analogous positions adopted by the Trp-1 and Phe-2, respectively. Trp-4 from WRPW overlies the side chains of Ile-3 and Leu-7 from eh1.

The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 22, 645-655) copyright 2006.

Figures were selected by the author.