Crystal structure of the conserved core of protein arginine methyltransferase PRMT3
Crystal structure of the conserved core of protein arginine methyltransferase PRMT3
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DOI：
10.1093/emboj/19.14.3509
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发表时间：
2000-07-17
期刊：
影响因子：
11.4
通讯作者：
Cheng, XD
中科院分区：
文献类型：
--
作者：
Zhang, X;Zhou, L;Cheng, XD
蛋白质精氨酸甲基化与信号转导、核运输和转录调控有关。蛋白质精氨酸甲基转移酶 (PRMT) 介导许多蛋白质的 AdoMet 依赖性甲基化，包括参与 RNA 加工和/或运输各个方面的许多 RNA 结合蛋白。在这里，我们描述了与反应产物 AdoIIcy 复合的大鼠 PRMT3 催化核心的晶体结构，在 2.0 埃分辨率下测定。结果揭示了两个结构域结构：AdoMet 结合结构域和桶状结构域。 AdoMet 结合结构域是 AdoMet 依赖性甲基转移酶共有折叠的紧凑版本。活性位点位于两个域之间的锥形口袋中。组成活性位点的残基在 PRMT 家族中是保守的，由含有两个不变 Glu 和一个 His-Asp 质子中继系统的双 E 环组成。该结构揭示了甲基化反应的机制，并为 PRMT 家族的功能表征提供了结构基础。此外，晶体堆积和溶液行为表明 PRMT3 核心形成了二聚体。
Protein arginine methylation has been implicated in signal transduction, nuclear transport and transcription regulation. Protein arginine methyltransferases (PRMTs) mediate the AdoMet-dependent methylation of many proteins, including many RNA binding proteins involved in various aspects of RNA processing and/or transport. Here we describe the crystal structure of the rat PRMT3 catalytic core in complex with reaction product AdoIIcy, determined at 2.0 Angstrom resolution. The results reveal a two-domain structure: an AdoMet-binding domain and a barrel-like domain. The AdoMet-binding domain is a compact version of the consensus AdoMet-dependent methyltransferase fold. The active site is situated in a cone-shaped pocket between the two domains. The residues that make up the active site are conserved across the PRMT family, consisting of a double-E loop containing two invariant Glu and one His-Asp proton-relay system. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the PRMT family. In addition, crystal packing and solution behavior suggest dimer formation of the PRMT3 core.