7KSO

Cryo-EM structure of PRC2:EZH1-AEBP2-JARID2

7KSO の概要

• エントリーDOI: 10.2210/pdb7kso/pdb
• EMDBエントリー: 23021
• 分子名称: Histone-lysine N-methyltransferase EZH1, Polycomb protein EED, Polycomb protein SUZ12, ... (7 entities in total)
• 機能のキーワード: chromatin, methyltransferase, nucleosome-modifying complex, gene regulation, gene regulation-transferase complex, gene regulation/transferase
• 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: 439068.94

構造登録者

Grau, D.J.,Armache, K.J. (登録日: 2020-11-23, 公開日: 2021-02-03, 最終更新日: 2024-03-06)

主引用文献

Grau, D.,Zhang, Y.,Lee, C.H.,Valencia-Sanchez, M.,Zhang, J.,Wang, M.,Holder, M.,Svetlov, V.,Tan, D.,Nudler, E.,Reinberg, D.,Walz, T.,Armache, K.J.
Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction.
Nat Commun, 12:714-714, 2021

PubMed Abstract: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin. Here, we present two cryo-EM structures of PRC2:EZH1, one as a monomer and a second one as a dimer bound to a nucleosome. When bound to nucleosome substrate, the PRC2:EZH1 dimer undergoes a dramatic conformational change. We demonstrate that mutation of a divergent EZH1/2 loop abrogates the nucleosome-binding and methyltransferase activities of PRC2:EZH1. Finally, we show that PRC2:EZH1 dimers are more effective than monomers at promoting chromatin compaction, and the divergent EZH1/2 loop is essential for this function, thereby tying together the methyltransferase, nucleosome-binding, and chromatin-compaction activities of PRC2:EZH1. We speculate that the conformational flexibility and the ability to dimerize enable PRC2 to act on the varied chromatin substrates it encounters in the cell.

PubMed: 33514705
DOI: 10.1038/s41467-020-20775-z

実験手法

ELECTRON MICROSCOPY (3.9 Å)