2AGH

Structural basis for cooperative transcription factor binding to the CBP coactivator

2AGH の概要

• エントリーDOI: 10.2210/pdb2agh/pdb
• NMR情報: BMRB: 6750
• 分子名称: Myb proto-oncogene protein, Crebbp protein, Zinc finger protein HRX (3 entities in total)
• 機能のキーワード: transcription
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Nucleus: P06876; Cytoplasm (By similarity): P45481; Nucleus. MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 16610.94

構造登録者

De Guzman, R.N.,Goto, N.K.,Dyson, H.J.,Wright, P.E. (登録日: 2005-07-26, 公開日: 2005-11-22, 最終更新日: 2024-05-01)

主引用文献

De Guzman, R.N.,Goto, N.K.,Dyson, H.J.,Wright, P.E.
Structural Basis for Cooperative Transcription Factor Binding to the CBP Coactivator
J.Mol.Biol., 355:1005-1013, 2006

PubMed Abstract: Regulation of transcription requires interactions between transcriptional activators and transcriptional co-activator CREB binding protein (CBP). The KIX domain of CBP can bind simultaneously to two different proteins, providing an additional mechanism for transcriptional regulation. Here we describe the solution structure of the ternary complex formed by cooperative binding of activation domains from the c-Myb and mixed lineage leukemia (MLL) transcription factors to the KIX domain. The MLL and c-Myb domains form helices that bind to two distinct hydrophobic grooves on opposite faces of KIX. Compared to the binary KIX:c-Myb complex, significant changes are observed in the structure of KIX at the MLL binding interface in the ternary complex. Two regions of KIX that are disordered in the binary complex become structured in the ternary complex: a flexible loop forms intimate contacts with bound MLL, and the C-terminal helix is extended and stabilized by MLL binding. This structural change results in the formation of additional electrostatic/polar interactions between KIX and the bound c-Myb, providing a structural basis for the cooperativity observed for the ternary complex.

PubMed: 16253272
DOI: 10.1016/j.jmb.2005.09.059

実験手法

SOLUTION NMR