Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Mol Biol. 2011 Nov 18;414(1):106-22. doi: 10.1016/j.jmb.2011.09.040. Epub 2011 Oct 1.
Protein arginine methyltransferase 10 (PRMT10) is a type I arginine methyltransferase that is essential for regulating flowering time in Arabidopsis thaliana. We present a 2.6 Å resolution crystal structure of A. thaliana PRMT 10 (AtPRMT10) in complex with a reaction product, S-adenosylhomocysteine. The structure reveals a dimerization arm that is 12-20 residues longer than PRMT structures elucidated previously; as a result, the essential AtPRMT10 dimer exhibits a large central cavity and a distinctly accessible active site. We employ molecular dynamics to examine how dimerization facilitates AtPRMT10 motions necessary for activity, and we show that these motions are conserved in other PRMT enzymes. Finally, functional data reveal that the 10 N-terminal residues of AtPRMT10 influence substrate specificity, and that enzyme activity is dependent on substrate protein sequences distal from the methylation site. Taken together, these data provide insights into the molecular mechanism of AtPRMT10, as well as other members of the PRMT family of enzymes. They highlight differences between AtPRMT10 and other PRMTs but also indicate that motions are a conserved element of PRMT function.
蛋白质精氨酸甲基转移酶 10（PRMT10）是一种Ⅰ型精氨酸甲基转移酶，对调控拟南芥开花时间至关重要。我们呈现了拟南芥 PRMT10（AtPRMT10）与反应产物 S-腺苷同型半胱氨酸复合物的 2.6Å 分辨率晶体结构。该结构揭示了一个二聚化臂，比之前解析的 PRMT 结构长 12-20 个残基；因此，必需的 AtPRMT10 二聚体表现出一个大的中央腔和一个明显可及的活性位点。我们采用分子动力学来研究二聚化如何促进 AtPRMT10 活性所需的运动，并且我们表明这些运动在其他 PRMT 酶中是保守的。最后，功能数据表明，AtPRMT10 的 10 个 N 端残基影响底物特异性，并且酶活性依赖于距甲基化位点较远的底物蛋白序列。总之，这些数据为 AtPRMT10 以及 PRMT 酶家族的其他成员的分子机制提供了深入了解。它们突出了 AtPRMT10 与其他 PRMT 之间的差异，但也表明运动是 PRMT 功能的一个保守元素。
