2YPB

Structure of the SCL:E47 complex bound to DNA

2YPB の概要

• エントリーDOI: 10.2210/pdb2ypb/pdb
• 関連するPDBエントリー: 1HLH 2YPA
• 分子名称: T-CELL ACUTE LYMPHOCYTIC LEUKEMIA PROTEIN 1, TRANSCRIPTION FACTOR E2-ALPHA, EBOX FORWARD, ... (4 entities in total)
• 機能のキーワード: immune system, hematopoiesis, leukemia
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus (By similarity): P17542; Nucleus: P15923
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 27101.75

構造登録者

El Omari, K.,Hoosdally, S.J.,Tuladhar, K.,Karia, D.,Ponsele, E.,Platonova, O.,Vyas, P.,Patient, R.,Porcher, C.,Mancini, E.J. (登録日: 2012-10-30, 公開日: 2013-07-31, 最終更新日: 2023-12-20)

主引用文献

El Omari, K.,Hoosdally, S.J.,Tuladhar, K.,Karia, D.,Hall-Ponsele, E.,Platonova, O.,Vyas, P.,Patient, R.,Porcher, C.,Mancini, E.J.
Structural Basis for Lmo2-Driven Recruitment of the Scl:E47bHLH Heterodimer to Hematopoietic-Specific Transcriptional Targets.
Cell Rep., 4:135-, 2013

PubMed Abstract: Cell fate is governed by combinatorial actions of transcriptional regulators assembling into multiprotein complexes. However, the molecular details of how these complexes form are poorly understood. One such complex, which contains the basic-helix-loop-helix heterodimer SCL:E47 and bridging proteins LMO2:LDB1, critically regulates hematopoiesis and induces T cell leukemia. Here, we report the crystal structure of (SCL:E47)bHLH:LMO2:LDB1LID bound to DNA, providing a molecular account of the network of interactions assembling this complex. This reveals an unexpected role for LMO2. Upon binding to SCL, LMO2 induces new hydrogen bonds in SCL:E47, thereby strengthening heterodimer formation. This imposes a rotation movement onto E47 that weakens the heterodimer:DNA interaction, shifting the main DNA-binding activity onto additional protein partners. Along with biochemical analyses, this illustrates, at an atomic level, how hematopoietic-specific SCL sequesters ubiquitous E47 and associated cofactors and supports SCL's reported DNA-binding-independent functions. Importantly, this work will drive the design of small molecules inhibiting leukemogenic processes.

PubMed: 23831025
DOI: 10.1016/J.CELREP.2013.06.008

実験手法

X-RAY DIFFRACTION (2.87 Å)