8T9G

Automethylated PRC2 dimer bound to nucleosome

これはPDB形式変換不可エントリーです。

8T9G の概要

• エントリーDOI: 10.2210/pdb8t9g/pdb
• EMDBエントリー: 41110
• 分子名称: Polycomb protein SUZ12, Histone H2B 1.1, DNA (226-MER), ... (13 entities in total)
• 機能のキーワード: histone methyl transferase, gene repression, epigenetics, chromatin, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 21
• 化学式量合計: 825687.67

構造登録者

Sauer, P.V.,Pavlenko, E.,Nogales, E.,Poepsel, S. (登録日: 2023-06-23, 公開日: 2024-09-25, 最終更新日: 2024-11-06)

主引用文献

Sauer, P.V.,Pavlenko, E.,Cookis, T.,Zirden, L.C.,Renn, J.,Singhal, A.,Hunold, P.,Hoehne-Wiechmann, M.N.,van Ray, O.,Kaschani, F.,Kaiser, M.,Hansel-Hertsch, R.,Sanbonmatsu, K.Y.,Nogales, E.,Poepsel, S.
Activation of automethylated PRC2 by dimerization on chromatin.
Mol.Cell, 84:3885-3898.e8, 2024

PubMed Abstract: Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric trans-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.

PubMed: 39303719
DOI: 10.1016/j.molcel.2024.08.025

実験手法

ELECTRON MICROSCOPY (6.2 Å)