6NZO

Set2 bound to nucleosome

6NZO の概要

• エントリーDOI: 10.2210/pdb6nzo/pdb
• EMDBエントリー: 0559
• 分子名称: Histone H3, Histone H4, Ubiquitin-60S ribosomal protein L40,Histone H2A, ... (8 entities in total)
• 機能のキーワード: set2, nucleosome, chromatin, kmt, gene regulation
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 326674.62

構造登録者

Halic, M.,Bilokapic, S. (登録日: 2019-02-14, 公開日: 2019-08-28, 最終更新日: 2019-09-04)

主引用文献

Bilokapic, S.,Halic, M.
Nucleosome and ubiquitin position Set2 to methylate H3K36.
Nat Commun, 10:3795-3795, 2019

PubMed Abstract: Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification deposited by the Set2 methyltransferases. Recent findings show that over-expression or mutation of Set2 enzymes promotes cancer progression, however, mechanisms of H3K36me are poorly understood. Set2 enzymes show spurious activity on histones and histone tails, and it is unknown how they obtain specificity to methylate H3K36 on the nucleosome. In this study, we present 3.8 Å cryo-EM structure of Set2 bound to the mimic of H2B ubiquitinated nucleosome. Our structure shows that Set2 makes extensive interactions with the H3 αN, the H3 tail, the H2A C-terminal tail and stabilizes DNA in the unwrapped conformation, which positions Set2 to specifically methylate H3K36. Moreover, we show that ubiquitin contributes to Set2 positioning on the nucleosome and stimulates the methyltransferase activity. Notably, our structure uncovers interfaces that can be targeted by small molecules for development of future cancer therapies.

PubMed: 31439846
DOI: 10.1038/s41467-019-11726-4

実験手法

ELECTRON MICROSCOPY (3.8 Å)