9IT4

Structure of Clr4 catalyzing histone H3 K9 methylation

9IT4 の概要

• エントリーDOI: 10.2210/pdb9it4/pdb
• 分子名称: Histone-lysine N-methyltransferase, H3 lysine-9 specific, Histone H3.1/H3.2, S-ADENOSYLMETHIONINE, ... (5 entities in total)
• 機能のキーワード: epigenetics, methylation, crosstalk, histone, gene regulation
• 由来する生物種: Schizosaccharomyces pombe 972h-; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36545.22

構造登録者

Du, Y.X.,Liu, L. (登録日: 2024-07-19, 公開日: 2025-04-30, 最終更新日: 2025-07-30)

主引用文献

Du, Y.,Sun, M.,Li, Z.,Wu, X.,Qu, Q.,Ai, H.,Liu, L.
Mechanistic insights into the stimulation of the histone H3K9 methyltransferase Clr4 by proximal H3K14 ubiquitination.
Sci Adv, 11:eadu1864-eadu1864, 2025

PubMed Abstract: H3K9 methylation, a conserved heterochromatin marker, is crucial for chromosome segregation and gene regulation. Clr4 is the sole known methyltransferase catalyzing H3K9 methylation in . Clr4 K455/K472 automethylation and H3K14 ubiquitination (H3K14Ub) are vital activators of Clr4, ensuring appropriate heterochromatin deposition and preventing deleterious silencing. While automethylation's activation mechanism is uncovered, the mechanism of H3K14Ub's significantly stronger stimulation on Clr4 remains unclear. Here, we determined the crystal structures of Clr4 bound to ubiquitinated and unmodified H3 peptides at 2.60 and 2.39 angstrom, which revealed a synergistic mechanism underlying the pronounced stimulatory effect: H3K14Ub increases substrate affinity through multivalent interactions and facilitates the allosteric transition of Clr4 from an inactive apo conformation to a hyperactive "catalyzing state," including conformational changes in the αC-SET-insertion region, autoregulatory loop, and the β9/10 loop. We finally propose a multilevel structural model for the Clr4 catalytic-regulatory cycle. This work provides structural insights into the interplay between histone modifications and their collective impact on epigenetic regulation.

PubMed: 40446033
DOI: 10.1126/sciadv.adu1864

実験手法

X-RAY DIFFRACTION (2.39 Å)