5T0M

A histone H3K9M mutation traps histone methyltransferase Clr4 to prevent heterochromatin spreading

5T0M の概要

• エントリーDOI: 10.2210/pdb5t0m/pdb
• 関連するPDBエントリー: 5T0K
• 分子名称: Histone-lysine N-methyltransferase EHMT2, THR-LYS-GLN-THR-ALA-ARG-NLE-SER-THR-GLY, ZINC ION, ... (6 entities in total)
• 機能のキーワード: histone methyltransferase, set domain, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 69725.70

構造登録者

Xu, K.,Tong, L. (登録日: 2016-08-16, 公開日: 2016-10-05, 最終更新日: 2024-10-30)

主引用文献

Shan, C.M.,Wang, J.,Xu, K.,Chen, H.,Yue, J.X.,Andrews, S.,Moresco, J.J.,Yates, J.R.,Nagy, P.L.,Tong, L.,Jia, S.
A histone H3K9M mutation traps histone methyltransferase Clr4 to prevent heterochromatin spreading.
Elife, 5:-, 2016

PubMed Abstract: Histone lysine-to-methionine (K-to-M) mutations are associated with multiple cancers, and they function in a dominant fashion to block the methylation of corresponding lysines on wild type histones. However, their mechanisms of function are controversial. Here we show that in fission yeast, introducing the K9M mutation into one of the three histone H3 genes dominantly blocks H3K9 methylation on wild type H3 across the genome. In addition, H3K9M enhances the interaction of histone H3 tail with the H3K9 methyltransferase Clr4 in a SAM (S-adenosyl-methionine)-dependent manner, and Clr4 is trapped at nucleation sites to prevent its spreading and the formation of large heterochromatin domains. We further determined the crystal structure of an H3K9M peptide in complex with human H3K9 methyltransferase G9a and SAM, which reveales that the methionine side chain had enhanced van der Waals interactions with G9a. Therefore, our results provide a detailed mechanism by which H3K9M regulates H3K9 methylation.

PubMed: 27648579
DOI: 10.7554/eLife.17903

実験手法

X-RAY DIFFRACTION (1.896 Å)