6AGO

Crystal structure of MRG15-ASH1L Histone methyltransferase complex

6AGO の概要

• エントリーDOI: 10.2210/pdb6ago/pdb
• 分子名称: Histone-lysine N-methyltransferase ASH1L, Mortality factor 4 like 1, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• 機能のキーワード: nucleosome, methylation, activation, regulation, gene regulation, transferase-gene regulation complex, transferase/gene regulation
• 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: 101005.38

構造登録者

Lee, Y.,Song, J. (登録日: 2018-08-13, 公開日: 2019-03-13, 最終更新日: 2024-03-27)

主引用文献

Lee, Y.,Yoon, E.,Cho, S.,Schmahling, S.,Muller, J.,Song, J.J.
Structural Basis of MRG15-Mediated Activation of the ASH1L Histone Methyltransferase by Releasing an Autoinhibitory Loop.
Structure, 27:846-, 2019

PubMed Abstract: Human ASH1L is the catalytic subunit of the conserved histone methyltransferase (HMTase) complex AMC that dimethylates lysine 36 in histone H3 (H3K36me2) to promote gene transcription in mammals and flies. Unlike AMC, ASH1L alone shows poor catalytic activity, because access to its substrate binding pocket is blocked by an autoinhibitory loop (AI loop) from the postSET domain. We report the crystal structure of the minimal catalytic active AMC complex containing ASH1L and its partner subunit MRG15. The structure reveals how binding of the MRG domain of MRG15 to a conserved FxLP motif in ASH1L results in the displacement of the AI loop to permit substrates to access the catalytic pocket of the ASH1L SET domain. Together, ASH1L activation by MRG15 therefore represents a delicate regulatory mechanism for how a cofactor activates an SET domain HMTase by releasing autoinhibition.

PubMed: 30827841
DOI: 10.1016/j.str.2019.01.016

実験手法

X-RAY DIFFRACTION (3.103 Å)