Structural Insight into Recognition of Methylated Histone H3K4 by Set3.
Structural Insight into Recognition of Methylated Histone H3K4 by Set3.
复制标题
DOI：
10.1016/j.jmb.2016.09.020
复制
发表时间：
2017-06-30
影响因子：
5.6
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
--
作者：
Gatchalian J;Ali M;Andrews FH;Zhang Y;Barrett AS;Kutateladze TG
Set 3的植物同源结构域（PHD）指在体外和体内结合组蛋白H3的甲基化赖氨酸4，然而该结构域的精确选择性尚未完全表征。在这里，我们探讨的决定因素甲基赖氨酸识别的PHD手指的Set 3和它的直系同源。我们使用X-射线晶体学和光谱学方法表明，Set 3 PHD手指结合二-和三甲基化状态的H3 K4具有可比的亲和力，并采用类似的分子机制与任一标记形成复合物。甲基赖氨酸结合口袋的组成在确定PHD指的选择性中起着至关重要的作用。组蛋白结合活性在Set 4的PHD指中不保守的发现表明Set 3和Set 4旁系同源物具有不同的功能。
The plant homeodomain (PHD) finger of Set3 binds methylated lysine 4 of histone H3 in vitro and in vivo, however precise selectivity of this domain has not been fully characterized. Here, we explore the determinants of methyllysine recognition by the PHD fingers of Set3 and its orthologs. We use X-ray crystallographic and spectroscopic approaches to show that the Set3 PHD finger binds di- and trimethylated states of H3K4 with comparable affinities and employs similar molecular mechanisms to form complexes with either mark. Composition of the methyllysine-binding pocket plays an essential role in determining the selectivity of the PHD fingers. The finding that the histone-binding activity is not conserved in the PHD finger of Set4 suggests different functions for the Set3 and Set4 paralogs.