5F59

The crystal structure of MLL3 SET domain

5F59 の概要

• エントリーDOI: 10.2210/pdb5f59/pdb
• 関連するPDBエントリー: 5F5E 5F6K 5F6L
• 分子名称: Histone-lysine N-methyltransferase 2C, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: histone methylation, histone methyltransferase, set domain, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : Q8NEZ4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18453.42

構造登録者

Li, Y.,Lei, M.,Chen, Y. (登録日: 2015-12-04, 公開日: 2016-02-24, 最終更新日: 2024-03-20)

主引用文献

Li, Y.,Han, J.,Zhang, Y.,Cao, F.,Liu, Z.,Li, S.,Wu, J.,Hu, C.,Wang, Y.,Shuai, J.,Chen, J.,Cao, L.,Li, D.,Shi, P.,Tian, C.,Zhang, J.,Dou, Y.,Li, G.,Chen, Y.,Lei, M.
Structural basis for activity regulation of MLL family methyltransferases.
Nature, 530:447-452, 2016

PubMed Abstract: The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.

PubMed: 26886794
DOI: 10.1038/nature16952

実験手法

X-RAY DIFFRACTION (2.801 Å)