6W5M

Cryo-EM structure of MLL1 in complex with RbBP5, WDR5, SET1, and ASH2L bound to the nucleosome (Class02)

6W5M の概要

• エントリーDOI: 10.2210/pdb6w5m/pdb
• EMDBエントリー: 21542 21543
• 分子名称: Retinoblastoma-binding protein 5, DNA (147-MER), WD repeat-containing protein 5, ... (10 entities in total)
• 機能のキーワード: mll1-ncp, h3k4 methylation, transferase, transferase-structural protein-dna complex, transferase/structural protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 377633.02

構造登録者

Park, S.H.,Lee, Y.T.,Ayoub, A.,Dou, Y.,Cho, U. (登録日: 2020-03-13, 公開日: 2021-03-31, 最終更新日: 2024-05-29)

主引用文献

Lee, Y.T.,Ayoub, A.,Park, S.H.,Sha, L.,Xu, J.,Mao, F.,Zheng, W.,Zhang, Y.,Cho, U.S.,Dou, Y.
Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin.
Nat Commun, 12:2953-2953, 2021

PubMed Abstract: Recent cryo-EM structures show the highly dynamic nature of the MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation of such dynamics remain unclear. Here we show that DPY30 and the intrinsically disordered regions (IDRs) of ASH2L work together in restricting the rotational dynamics of the MLL1 complex on the NCP. We show that DPY30 binding to ASH2L leads to stabilization and integration of ASH2L IDRs into the MLL1 complex and establishes new ASH2L-NCP contacts. The significance of ASH2L-DPY30 interactions is demonstrated by requirement of both ASH2L IDRs and DPY30 for dramatic increase of processivity and activity of the MLL1 complex. This DPY30 and ASH2L-IDR dependent regulation is NCP-specific and applies to all members of the MLL/SET1 family of enzymes. We further show that DPY30 is causal for de novo establishment of H3K4me3 in ESCs. Our study provides a paradigm of how H3K4me3 is regulated on chromatin and how H3K4me3 heterogeneity can be modulated by ASH2L IDR interacting proteins.

PubMed: 34012049
DOI: 10.1038/s41467-021-23268-9

実験手法

ELECTRON MICROSCOPY (4.6 Å)