3P4F

Structural and biochemical insights into MLL1 core complex assembly and regulation.

3P4F の概要

• エントリーDOI: 10.2210/pdb3p4f/pdb
• 関連するPDBエントリー: 2H14
• 分子名称: WD repeat-containing protein 5, Retinoblastoma-binding protein 5, Histone-lysine N-methyltransferase MLL, ... (4 entities in total)
• 機能のキーワード: beta-propeller, scaffold, mll1, rbbp5, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : P61964 Q15291; 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: 37054.84

構造登録者

Avdic, V.,Zhang, P.,Lanouette, S.,Groulx, A.,Tremblay, V.,Brunzelle, J.B.,Couture, J.-F. (登録日: 2010-10-06, 公開日: 2010-12-08, 最終更新日: 2023-09-06)

主引用文献

Avdic, V.,Zhang, P.,Lanouette, S.,Groulx, A.,Tremblay, V.,Brunzelle, J.,Couture, J.-F.
Structural and biochemical insights into MLL1 core complex assembly.
Structure, 19:101-108, 2011

PubMed Abstract: Histone H3 Lys-4 methylation is predominantly catalyzed by a family of methyltransferases whose enzymatic activity depends on their interaction with a three-subunit complex composed of WDR5, RbBP5, and Ash2L. Here, we report that a segment of 50 residues of RbBP5 bridges the Ash2L C-terminal domain to WDR5. The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5's β-propeller domain. RbBP5 engages in several hydrogen bonds and van der Waals contacts within a V-shaped cleft formed by the junction of two blades on WDR5. Mutational analyses of both the WDR5 V-shaped cleft and RbBP5 residues reveal that the interactions between RbBP5 and WDR5 are important for the stimulation of MLL1 methyltransferase activity. Overall, this study provides the structural basis underlying the formation of the WDR5-RbBP5 subcomplex and further highlight the crucial role of WDR5 in scaffolding the MLL1 core complex.

PubMed: 21220120
DOI: 10.1016/j.str.2010.09.022

実験手法

X-RAY DIFFRACTION (2.35 Å)