Institute of Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Strasse 3, D-06120 Halle, Germany.
Biol Chem. 2013 Aug;394(8):1029-43. doi: 10.1515/hsz-2013-0121.
Asymmetric dimethylation of arginine side chains in proteins is a frequent posttranslational modification, catalyzed by type I protein arginine methyltransferases (PRMTs). This article summarizes what is known about this modification in the nuclear poly(A)-binding protein (PABPN1). PABPN1 contains 13 dimethylated arginine residues in its C-terminal domain. Three enzymes, PRMT1, 3, and 6, can methylate PABPN1. Although 26 methyl groups are transferred to one PABPN1 molecule, the PRMTs do so in a distributive reaction, i.e., only a single methyl group is transferred per binding event. As PRMTs form dimers, with the active sites accessible from a small central cavity, backbone conformation around the methyl-accepting arginine is an important determinant of substrate specificity. Neither the association of PABPN1 with poly(A) nor its role in poly(A) tail synthesis is affected by arginine methylation. At least at low protein concentration, methylation does not affect the protein's tendency to oligomerize. The dimethylarginine residues of PABPN1 are located in the binding site for its nuclear import receptor, transportin. Arginine methylation weakens this interaction about 10-fold. Very recent evidence suggests that arginine methylation as a way of fine-tuning the interactions between transportin and its cargo may be a general mechanism.
蛋白质精氨酸侧链的不对称二甲基化是一种常见的翻译后修饰，由 I 型蛋白精氨酸甲基转移酶（PRMTs）催化。本文总结了核多聚（A）结合蛋白（PABPN1）中这种修饰的已知情况。PABPN1 的 C 末端结构域含有 13 个二甲基精氨酸残基。三种酶，PRMT1、3 和 6，可以甲基化 PABPN1。虽然 26 个甲基基团被转移到一个 PABPN1 分子上，但 PRMTs 以分散反应的方式进行，即在每个结合事件中只转移一个甲基基团。由于 PRMTs 形成二聚体，活性位点可从一个小的中央腔进入，因此接受甲基的精氨酸的骨架构象是决定底物特异性的重要因素。PABPN1 与多聚（A）的结合及其在多聚（A）尾巴合成中的作用均不受精氨酸甲基化的影响。至少在低蛋白浓度下，甲基化不会影响蛋白质的寡聚倾向。PABPN1 的二甲基精氨酸残基位于其核输入受体、转导蛋白的结合位点。精氨酸甲基化使这种相互作用减弱约 10 倍。最近的证据表明，作为精细调节转导蛋白与其货物之间相互作用的一种方式，精氨酸甲基化可能是一种普遍的机制。
