4L18

Crystal structure of Runx1 and Ets1 bound to TCR alpha promoter (crystal form 3)

4L18 の概要

• エントリーDOI: 10.2210/pdb4l18/pdb
• 関連するPDBエントリー: 4L0Y 4L0Z
• 分子名称: Runt-related transcription factor 1, Protein C-ets-1, 5'-D(*GP*GP*AP*AP*GP*CP*CP*AP*CP*AP*TP*CP*CP*TP*CP*T)-3', ... (6 entities in total)
• 機能のキーワード: runt domain, ets domain, transcription-dna complex, transcription/dna
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Nucleus: Q03347; Cytoplasm: P14921
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 91116.27

構造登録者

Tahirov, T.H. (登録日: 2013-06-02, 公開日: 2014-03-26, 最終更新日: 2024-02-28)

主引用文献

Shrivastava, T.,Mino, K.,Babayeva, N.D.,Baranovskaya, O.I.,Rizzino, A.,Tahirov, T.H.
Structural basis of Ets1 activation by Runx1.
Leukemia, 28:2040-2048, 2014

PubMed Abstract: Runx1 is required for definitive hematopoiesis and is well known for its frequent chromosomal translocations and point mutations in leukemia. Runx1 regulates a variety of genes via Ets1 activation on an Ets1•Runx1 composite DNA sequence. The structural basis of such regulation remains unresolved. To address this problem, we determined the crystal structure of the ternary complex containing Runx1(1-242) and Ets1(296-441) bound to T-cell receptor alpha (TCRα) enhancer DNA. In the crystal, an Ets1-interacting domain of Runx1 is bound to the Ets1 DNA-binding domain and displaced an entire autoinhibitory module of Ets1, revealing a novel mechanism of Ets1 activation. The DNA-binding and transcriptional studies with a variety of structure-guided Runx1 mutants confirmed a critical role of direct Ets1•Runx1 interaction in Ets1 activation. More importantly, the discovered mechanism provides a plausible explanation for how the Ets1•Runx1 interaction effectively activates not only a wild-type Ets1, but also a highly inhibited phosphorylated form of Ets1.

PubMed: 24646888
DOI: 10.1038/leu.2014.111

実験手法

X-RAY DIFFRACTION (2.3 Å)