Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains

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...

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Published in:	The Journal of biological chemistry Vol. 290; no. 49; pp. 29313 - 29328
Main Authors:	Cho, Ha Yeon, Maeng, Seo Jin, Cho, Hyo Je, Choi, Yoon Seo, Chung, Jeong Min, Lee, Sangmin, Kim, Hoi Kyoung, Kim, Jong Hyun, Eom, Chi-Yong, Kim, Yeon-Gil, Guo, Min, Jung, Hyun Suk, Kang, Beom Sik, Kim, Sunghoon
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 04-12-2015 American Society for Biochemistry and Molecular Biology
Subjects:	Amino Acid Sequence Amino Acyl-tRNA Synthetases - chemistry aminoacyl tRNA synthetase Animals CHO Cells Chromatography Cricetinae Cricetulus crystal structure Fluorescence Resonance Energy Transfer glutathione transferase Glutathione Transferase - chemistry Humans Methionine-tRNA Ligase - chemistry Microscopy, Electron Molecular Sequence Data multi-tRNA synthetase complex Multiprotein Complexes Nuclear Proteins - chemistry Peptide Elongation Factors - chemistry Protein Conformation Protein Interaction Mapping protein structure Protein Structure and Folding Protein Structure, Tertiary protein-protein interaction scaffold protein Sequence Homology, Amino Acid Signal Transduction Tumor Suppressor Proteins - chemistry protein structure glutathione transferase multi-tRNA synthetase complex aminoacyl tRNA synthetase crystal structure scaffold protein protein-protein interaction
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Summary:	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 MSC components, 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. Background: GST domains have been found in diverse proteins involved in translational systems. Results: Four GST domains from human methionyl-tRNA synthetase, glutaminyl-prolyl-tRNA synthetase, ARS-interacting multifunctional protein (AIMP) 2, and AIMP3 are complexed in an ordered fashion. Conclusion: Four components in the human multisynthetase complex are assembled through a GST domain tetrameric complex. Significance: GST domain assemblies act as scaffolds for the formation of multicomponent protein complexes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.M115.690867