4OM3

Crystal structure of human TLE1 Q-domain residues 20-156

Summary for 4OM3

• Entry DOI: 10.2210/pdb4om3/pdb
• Related: 4om2
• Descriptor: Transducin-like enhancer protein 1, GLYCEROL (2 entities in total)
• Functional Keywords: tetramer, helix-turn-helix, wnt repressor, tcf/lef, transcription, dna binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q04724
• Total number of polymer chains: 4
• Total formula weight: 66792.25

Authors

Chodaparambil, J.V.,Weis, W.I. (deposition date: 2014-01-25, release date: 2014-04-09, Last modification date: 2024-02-28)

Primary citation

Chodaparambil, J.V.,Pate, K.T.,Hepler, M.R.,Tsai, B.P.,Muthurajan, U.M.,Luger, K.,Waterman, M.L.,Weis, W.I.
Molecular functions of the TLE tetramerization domain in Wnt target gene repression.
Embo J., 33:719-731, 2014

PubMed Abstract: Wnt signaling activates target genes by promoting association of the co-activator β-catenin with TCF/LEF transcription factors. In the absence of β-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 β-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.

PubMed: 24596249
DOI: 10.1002/embj.201387188

Experimental method

X-RAY DIFFRACTION (2.855 Å)