3UVK

Crystal structure of WDR5 in complex with the WDR5-interacting motif of MLL2

3UVK の概要

• エントリーDOI: 10.2210/pdb3uvk/pdb
• 関連するPDBエントリー: 3UVL 3UVM 3UVN 3UVO
• 分子名称: WD repeat-containing protein 5, Histone-lysine N-methyltransferase MLL2, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• 機能のキーワード: trithorax, chromatin biology, beta-propeller, scaffolding, histone h3, nucleus, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P61964; Nucleus (Probable): O14686
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36276.14

構造登録者

Zhang, P.,Lee, H.,Brunzelle, J.S.,Couture, J.-F. (登録日: 2011-11-30, 公開日: 2011-12-14, 最終更新日: 2023-09-13)

主引用文献

Zhang, P.,Lee, H.,Brunzelle, J.S.,Couture, J.F.
The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases.
Nucleic Acids Res., 40:4237-4246, 2012

PubMed Abstract: In mammals, the SET1 family of lysine methyltransferases (KMTs), which includes MLL1-5, SET1A and SET1B, catalyzes the methylation of lysine-4 (Lys-4) on histone H3. Recent reports have demonstrated that a three-subunit complex composed of WD-repeat protein-5 (WDR5), retinoblastoma-binding protein-5 (RbBP5) and absent, small, homeotic disks-2-like (ASH2L) stimulates the methyltransferase activity of MLL1. On the basis of studies showing that this stimulation is in part controlled by an interaction between WDR5 and a small region located in close proximity of the MLL1 catalytic domain [referred to as the WDR5-interacting motif (Win)], it has been suggested that WDR5 might play an analogous role in scaffolding the other SET1 complexes. We herein provide biochemical and structural evidence showing that WDR5 binds the Win motifs of MLL2-4, SET1A and SET1B. Comparative analysis of WDR5-Win complexes reveals that binding of the Win motifs is achieved by the plasticity of WDR5 peptidyl-arginine-binding cleft allowing the C-terminal ends of the Win motifs to be maintained in structurally divergent conformations. Consistently, enzymatic assays reveal that WDR5 plays an important role in the optimal stimulation of MLL2-4, SET1A and SET1B methyltransferase activity by the RbBP5-ASH2L heterodimer. Overall, our findings illustrate the function of WDR5 in scaffolding the SET1 family of KMTs and further emphasize on the important role of WDR5 in regulating global histone H3 Lys-4 methylation.

PubMed: 22266653
DOI: 10.1093/nar/gkr1235

実験手法

X-RAY DIFFRACTION (1.4 Å)