3OS5

SET7/9-Dnmt1 K142me1 complex

3OS5 の概要

• エントリーDOI: 10.2210/pdb3os5/pdb
• 関連するPDBエントリー: 3CBM 3CBO 3CBP
• 分子名称: Histone-lysine N-methyltransferase SETD7, Dnmt1, BETA-MERCAPTOETHANOL, ... (7 entities in total)
• 機能のキーワード: epigenetic modification, set domain, protein lysine methyltransferase, dnmt1, lysine mono-methylation, k142, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q8WTS6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30254.72

構造登録者

Esteve, P.-O.,Chang, Y.,Samaranayake, M.,Upadhyay, A.K.,Horton, J.R.,Feehery, G.R.,Cheng, X.,Pradhan, S. (登録日: 2010-09-08, 公開日: 2010-12-15, 最終更新日: 2023-09-06)

主引用文献

Esteve, P.O.,Chang, Y.,Samaranayake, M.,Upadhyay, A.K.,Horton, J.R.,Feehery, G.R.,Cheng, X.,Pradhan, S.
A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability.
Nat.Struct.Mol.Biol., 18:42-48, 2011

PubMed Abstract: The protein lysine methyltransferase SET7 regulates DNA methyltransferase-1 (DNMT1) activity in mammalian cells by promoting degradation of DNMT1 and thus allows epigenetic changes via DNA demethylation. Here we reveal an interplay between monomethylation of DNMT1 Lys142 by SET7 and phosphorylation of DNMT1 Ser143 by AKT1 kinase. These two modifications are mutually exclusive, and structural analysis suggests that Ser143 phosphorylation interferes with Lys142 monomethylation. AKT1 kinase colocalizes and directly interacts with DNMT1 and phosphorylates Ser143. Phosphorylated DNMT1 peaks during DNA synthesis, before DNMT1 methylation. Depletion of AKT1 or overexpression of dominant-negative AKT1 increases methylated DNMT1, resulting in a decrease in DNMT1 abundance. In mammalian cells, phosphorylated DNMT1 is more stable than methylated DNMT1. These results reveal cross-talk on DNMT1, through modifications mediated by AKT1 and SET7, that affects cellular DNMT1 levels.

PubMed: 21151116
DOI: 10.1038/nsmb.1939

実験手法

X-RAY DIFFRACTION (1.69 Å)