摘要
Euchromatic histone-lysine N-methyltransferase 1 (EHMT1; G9a-like protein; GLP) and euchromatic histone-lysine N-methyltransferase 2 (EHMT2; G9a) are protein lysine methyltransferases that regulate gene expression and are essential for development and the ability of organisms to change and adapt. In addition to ankyrin repeats and the catalytic SET domain, the EHMT proteins contain a unique cysteine-rich region (CRR) that mediates protein–protein interactions and recruitment of the methyltransferases to specific sites in chromatin. We have determined the structure of the CRR from human EHMT2 by X-ray crystallography and show that the CRR adopts an unusual compact fold with four bound zinc atoms. The structure consists of a RING domain preceded by a smaller zinc-binding motif and an N-terminal segment. The smaller zinc-binding motif straddles the N-terminal end of the RING domain, and the N-terminal segment runs in an extended conformation along one side of the structure and interacts with both the smaller zinc-binding motif and the RING domain. The interface between the N-terminal segment and the RING domain includes one of the zinc atoms. The RING domain is partially sequestered within the CRR and unlikely to function as a ubiquitin ligase.
摘要译文
欧氏族组蛋白 - 赖氨酸N-甲基转移酶1（EHMT1; g9a样蛋白质; GLP）和欧氏族组蛋白 - 赖氨酸N-甲基转移酶2（EHMT2; G9A）是蛋白质赖氨酸甲基转移酶，其调节基因表达，对发育至关重要，并且生物体改变和适应的能力是必不可少的。除了Ankyrin重复和催化设定结构域之外，EHMT蛋白质含有独特的富含半胱氨酸的区域（CRR），其介导蛋白质 - 蛋白质相互作用和募集甲基转移酶在染色质的特定位点。我们已经通过X射线晶体学确定了来自人EHMT2的CRR的结构，并表明CRR采用具有四个结合的锌原子的异常紧凑型。该结构由较小的锌结合基序和N末端段之前的环结构域组成。较小的锌绑定基序横跨环形结构域的n末端端部，N-末端段沿着结构的一侧延伸并与较小的锌结合基序和环结构域相互作用。 n末端段和环结构域之间的界面包括锌原子之一。环形结构域在CRR内部被隔离，并且不太可能用作泛素连接酶。
Keshia M.Kerchner[a];Tung-ChungMou[b][c];YizhiSun[a];Domniţa-ValeriaRusnac[a];Stephen R.Sprang[b][c]. The structure of the cysteine-rich region from human histone-lysine N-methyltransferase EHMT2 (G9a)[J]. Journal of Structural Biology: X, 2021,5