7BRE

The crystal structure of MLL2 in complex with ASH2L and RBBP5

7BRE の概要

• エントリーDOI: 10.2210/pdb7bre/pdb
• 分子名称: Set1/Ash2 histone methyltransferase complex subunit ASH2, Histone-lysine N-methyltransferase 2B, Retinoblastoma-binding protein 5, ... (5 entities in total)
• 機能のキーワード: histone methyltransferase, mll2 complex, mll2, rbbp5, ash2l, histone methylation, epigenetics, protein binding, non-histone substrate, p53
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 86679.29

構造登録者

Li, Y.,Zhao, L.,Chen, Y. (登録日: 2020-03-28, 公開日: 2020-07-22, 最終更新日: 2023-11-29)

主引用文献

Li, Y.,Zhao, L.,Tian, X.,Peng, C.,Gong, F.,Chen, Y.
Crystal Structure of MLL2 Complex Guides the Identification of a Methylation Site on P53 Catalyzed by KMT2 Family Methyltransferases.
Structure, 28:1141-, 2020

PubMed Abstract: KMT2 family methyltransferases methylate histone H3 lysine 4 and play essential roles in multiple cellular processes. MLL2 (KMT2B) is required for early epigenetic decisions during development and contributes to the methylation of bivalent promoters. Here, we determined the crystal structure of the MLL2-RBBP5-ASH2L complex and confirmed that RBBP5-ASH2L was essential for activating the MLL2 SET domain through a conserved mechanism across KMT2 family complexes. In the MLL2 complex structure, a short N-terminal loop of MLL2 adopts a similar configuration of the H3 peptide and inserts into the substrate-binding pocket of another MLL2, indicating a potential substrate for MLL2. We identify that P53 contains a sequence similar to the N-terminal loop of MLL2, and demonstrate that K305 of P53 could be methylated by KMT2 family complexes except for SET1A. Our results provide an important implication of functional interplay between P53 and KMT2 family complexes, and also suggest the possible broad landscape of non-histone substrate for KMT2 family methyltransferases.

PubMed: 32697937
DOI: 10.1016/j.str.2020.07.002

実験手法

X-RAY DIFFRACTION (2.803 Å)