4OM2: Crystal Structure Of Tle1 N-terminal Q-domain Residues 1-156

Wnt signaling activates target genes by promoting association of the co-activator beta-catenin with TCF/LEF transcription factors. In the absence of beta-catenin, target genes are silenced by TCF-mediated recruitment of TLE/Groucho proteins, but the molecular basis for TLE/TCF-dependent repression is unclear. We describe the unusual three-dimensional structure of the N-terminal Q domain of TLE1 that mediates tetramerization and binds to TCFs. We find that differences in repression potential of TCF/LEFs correlates with their affinities for TLE-Q, rather than direct competition between beta-catenin and TLE for TCFs as part of an activation-repression switch. Structure-based mutation of the TLE tetramer interface shows that dimers cannot mediate repression, even though they bind to TCFs with the same affinity as tetramers. Furthermore, the TLE Q tetramer, not the dimer, binds to chromatin, specifically to K20 methylated histone H4 tails, suggesting that the TCF/TLE tetramer complex promotes structural transitions of chromatin to mediate repression.
PDB ID: 4OM2Download
MMDB ID: 119065
PDB Deposition Date: 2014/1/25
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 4  Å
Source Organism:
Similar Structures:
Biological Unit for 4OM2: tetrameric; determined by author and by software (PISA)
Molecular Components in 4OM2
Label Count Molecule
Proteins (4 molecules)
Transducin-like Enhancer Protein 1(Gene symbol: TLE1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB