3N71

Crystal structure of cardiac specific histone methyltransferase SmyD1

3N71 の概要

• エントリーDOI: 10.2210/pdb3n71/pdb
• 分子名称: Histone lysine methyltransferase SmyD1, SINEFUNGIN, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (6 entities in total)
• 機能のキーワード: histone lysine methyltransferase, smyd1, heart development, mynd, transcription
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57533.74

構造登録者

Sirinupong, N.,Yang, Z. (登録日: 2010-05-26, 公開日: 2010-10-13, 最終更新日: 2024-02-21)

主引用文献

Sirinupong, N.,Brunzelle, J.,Ye, J.,Pirzada, A.,Nico, L.,Yang, Z.
Crystal Structure of Cardiac-specific Histone Methyltransferase SmyD1 Reveals Unusual Active Site Architecture.
J.Biol.Chem., 285:40635-40644, 2010

PubMed Abstract: SmyD1 is a cardiac- and muscle-specific histone methyltransferase that methylates histone H3 at lysine 4 and regulates gene transcription in early heart development. The unique domain structure characterized by a "split" SET domain, a conserved MYND zinc finger, and a novel C-terminal domain (CTD) distinguishes SmyD1 from other SET domain containing methyltransferases. Here we report the crystal structure of full-length SmyD1 in complex with the cofactor analog sinefungin at 2.3 Å. The structure reveals that SmyD1 folds into a wrench-shaped structure with two thick "grips" separated by a large, deep concave opening. Importantly, our structural and functional analysis suggests that SmyD1 appears to be regulated by an autoinhibition mechanism, and that unusually spacious target lysine-access channel and the presence of the CTD domain both negatively contribute to the regulation of this cardiovascularly relevant methyltransferase. Furthermore, our structure also provides a structural basis for the interaction between SmyD1 and cardiac transcription factor skNAC, and suggests that the MYND domain may primarily serve as a protein interaction module and cooperate SmyD1 with skNAC to regulate cardiomyocyte growth and maturation. Overall, our data provide novel insights into the mechanism of SmyD1 regulation, which would be helpful in further understanding the role of this protein in heart development and cardiovascular diseases.

PubMed: 20943667
DOI: 10.1074/jbc.M110.168187

実験手法

X-RAY DIFFRACTION (2.3 Å)