Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains
Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains
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DOI：
10.1074/jbc.m115.690867
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发表时间：
2015-12-04
影响因子：
4.8
通讯作者：
Kim, Sunghoon
中科院分区：
文献类型：
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作者：
Cho, Ha Yeon;Maeng, Seo Jin;Kim, Sunghoon
许多多组分蛋白质复合物介导不同的细胞过程组装通过支架与专门的蛋白质相互作用模块。多tRNA合成酶复合物（MSC）由9种不同的氨酰-tRNA合成酶和3种非酶因子（AIMP 1 -3）组成，除了在蛋白质合成中发挥作用外，还充当许多信号通路的枢纽。然而，MSC组件的组装过程和结构布置并不清楚。在这里，我们显示了四个MSC组件，甲硫氨酰-tRNA合成酶（MRS），氨甲酰基-脯氨酰-tRNA合成酶（EPRS），AIMP 2和AIMP 3之间共享的谷胱甘肽转移酶（GST）结构域的异四聚体复合物结构。使用界面1的MRS-AIMP 3和EPRS-AIMP 2经由AIMP 3和EPRS的界面2桥接，以生成摩尔比为（1：1）：（1：1）的MRS-AIMP 3：EPRS-AIMP 2的独特线性复合物。有趣的是，AIMP 3：EPRS在界面2处的亲和力可以根据界面1的占据率而变化，这表明线性GST四聚体的动态性质。这四个组件被优化排列，以最大限度地容纳额外的结构域和蛋白质。这些特征表明GST四聚体是一种独特的动态结构平台，MSC组件由其组装而成。考虑到GST样结构域的流行，这种四聚体也可以提供MSC与其他含GST的细胞因子通讯的工具。
Many multicomponent protein complexes mediating diverse cellular processes are assembled through scaffolds with specialized protein interaction modules. The multi-tRNA synthetase complex (MSC), consisting of nine different aminoacyl-tRNA synthetases and three non-enzymatic factors (AIMP1-3), serves as a hub for many signaling pathways in addition to its role in protein synthesis. However, the assembly process and structural arrangement of the MSC components are not well understood. Here we show the heterotetrameric complex structure of the glutathione transferase (GST) domains shared among the four MSCcomponents, methionyl-tRNA synthetase (MRS), glutaminyl-prolyl-tRNA synthetase (EPRS), AIMP2 and AIMP3. The MRS-AIMP3 and EPRS-AIMP2 using interface 1 are bridged via interface 2 of AIMP3 and EPRS to generate a unique linear complex of MRS-AIMP3: EPRS-AIMP2 at the molar ratio of (1: 1):(1: 1). Interestingly, the affinity at interface 2 of AIMP3: EPRS can be varied depending on the occupancy of interface 1, suggesting the dynamic nature of the linear GST tetramer. The four components are optimally arranged for maximal accommodation of additional domains and proteins. These characteristics suggest the GST tetramer as a unique and dynamic structural platform from which the MSC components are assembled. Considering prevalence of the GST-like domains, this tetramer can also provide a tool for the communication of the MSC with other GST-containing cellular factors.