4OM2

Crystal structure of TLE1 N-terminal Q-domain residues 1-156

4OM2 の概要

• エントリーDOI: 10.2210/pdb4om2/pdb
• 関連するPDBエントリー: 4OM3
• 分子名称: Transducin-like enhancer protein 1 (1 entity in total)
• 機能のキーワード: tetramer, helix-turn-helix, wnt repressor, tcf/lef, transcription, dna binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q04724
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 73708.01

構造登録者

Chodaparambil, J.V.,Weis, W.I. (登録日: 2014-01-25, 公開日: 2014-04-09, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

X-RAY DIFFRACTION (4 Å)