4X8P

Crystal structure of Ash2L SPRY domain in complex with RbBP5

4X8P の概要

• エントリーDOI: 10.2210/pdb4x8p/pdb
• 関連するPDBエントリー: 4X8N
• 分子名称: Set1/Ash2 histone methyltransferase complex subunit ASH2,Set1/Ash2 histone methyltransferase complex subunit ASH2, Retinoblastoma-binding protein 5, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: histone, mll1, epigenetics, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q9UBL3 Q15291
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22076.83

構造登録者

Zhang, P.,Chaturvedi, C.P.,Brunzelle, J.S.,Skiniotis, G.,Brand, M.,Shilatifard, A.,Couture, J.-F. (登録日: 2014-12-10, 公開日: 2015-01-28, 最終更新日: 2024-02-28)

主引用文献

Zhang, P.,Chaturvedi, C.P.,Tremblay, V.,Cramet, M.,Brunzelle, J.S.,Skiniotis, G.,Brand, M.,Shilatifard, A.,Couture, J.F.
A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation.
Genes Dev., 29:123-128, 2015

PubMed Abstract: The methyltransferase activity of the trithorax group (TrxG) protein MLL1 found within its COMPASS (complex associated with SET1)-like complex is allosterically regulated by a four-subunit complex composed of WDR5, RbBP5, Ash2L, and DPY30 (also referred to as WRAD). We report structural evidence showing that in WRAD, a concave surface of the Ash2L SPIa and ryanodine receptor (SPRY) domain binds to a cluster of acidic residues, referred to as the D/E box, in RbBP5. Mutational analysis shows that residues forming the Ash2L/RbBP5 interface are important for heterodimer formation, stimulation of MLL1 catalytic activity, and erythroid cell terminal differentiation. We also demonstrate that a phosphorylation switch on RbBP5 stimulates WRAD complex formation and significantly increases KMT2 (lysine [K] methyltransferase 2) enzyme methylation rates. Overall, our findings provide structural insights into the assembly of the WRAD complex and point to a novel regulatory mechanism controlling the activity of the KMT2/COMPASS family of lysine methyltransferases.

PubMed: 25593305
DOI: 10.1101/gad.254870.114

実験手法

X-RAY DIFFRACTION (2.2 Å)