5TQR

ctPRC2 in an autoinhibited conformation bound to S-adenosylmethionine

5TQR の概要

• エントリーDOI: 10.2210/pdb5tqr/pdb
• 関連するPDBエントリー: 5BJS 5VK3
• 分子名称: Polycomb Protein EED, Histone-lysine N-methyltransferase EZH2, Polycomb protein SUZ12, ZINC ION, ... (5 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Chaetomium thermophilum; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 173812.68

構造登録者

Bratkowski, M.A.,Liu, X. (登録日: 2016-10-24, 公開日: 2017-06-14, 最終更新日: 2023-10-04)

主引用文献

Bratkowski, M.,Yang, X.,Liu, X.
Polycomb repressive complex 2 in an autoinhibited state.
J. Biol. Chem., 292:13323-13332, 2017

PubMed Abstract: Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo-PRC2 from the fungus captured in a autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously. We found that binding by the cofactor -adenosylmethionine mitigates this autoinhibited structural state. Using steady-state enzyme kinetics, we also demonstrated that disrupting the autoinhibition results in a vastly activated enzyme complex. Autoinhibition provides a novel structural platform that may enable control of PRC2 activity in response to diverse transcriptional states and chromatin contexts and set a ground state to allow PRC2 activation by other cellular mechanisms as well.

PubMed: 28607149
DOI: 10.1074/jbc.M117.787572

実験手法

X-RAY DIFFRACTION (2.571 Å)