title: Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains.
abstract: 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.
authors.affiliation: From the School of Life Science and Biotechnology, KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Ha Yeon
authors.initials: HY
authors.lastname: Cho
authors.affiliation: From the School of Life Science and Biotechnology, KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Maeng
authors.affiliation: From the School of Life Science and Biotechnology, KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Hyo Je
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: From the School of Life Science and Biotechnology, KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Yoon Seo
authors.initials: YS
authors.lastname: Choi
authors.affiliation: the Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Chung
authors.affiliation: the Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Lee
authors.affiliation: the Department of Molecular Medicine and Biopharmaceutical Sciences, Medicinal Bioconvergence Research Center, Graduate School of Convergence Technology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hoi Kyoung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: the Department of Molecular Medicine and Biopharmaceutical Sciences, Medicinal Bioconvergence Research Center, Graduate School of Convergence Technology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: the NanoBio Convergence Research Team, Western Seoul Center, Korea Basic Science Institute, Seoul 120-750, Korea.
authors.forename: Chi-Yong
authors.initials: CY
authors.lastname: Eom
authors.affiliation: the Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang 790-834, Korea.
authors.forename: Yeon-Gil
authors.initials: YG
authors.lastname: Kim
authors.affiliation: the Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, and.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.affiliation: the Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Jung
authors.affiliation: From the School of Life Science and Biotechnology, KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Korea, bskang2@knu.ac.kr.
authors.forename: Beom Sik
authors.initials: BS
authors.lastname: Kang
authors.affiliation: the Department of Molecular Medicine and Biopharmaceutical Sciences, Medicinal Bioconvergence Research Center, Graduate School of Convergence Technology, Seoul National University, Seoul 151-742, Korea, the The National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai 201203, China sungkim@snu.ac.kr.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D002845:Chromatography; D006224:Cricetinae; D003412:Cricetulus; D031541:Fluorescence Resonance Energy Transfer; D005982:Glutathione Transferase / Q000737:chemistry*; D006801:Humans; D008718:Methionine-tRNA Ligase / Q000737:chemistry*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000737:chemistry*; D010445:Peptide Elongation Factors / Q000737:chemistry*; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000737:chemistry*
chemical_list: C575685:AIMP2 protein, human; C529799:EEF1E1 protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D025521:Tumor Suppressor Proteins; D005982:Glutathione Transferase; D000604:Amino Acyl-tRNA Synthetases; C415462:glutamyl-prolyl-tRNA synthetase; D008718:Methionine-tRNA Ligase; C100134:prolyl T RNA synthetase; C020659:glutaminyl-tRNA synthetase
keywords: aminoacyl tRNA synthetase; crystal structure; glutathione transferase; multi-tRNA synthetase complex; protein structure; protein-protein interaction; scaffold protein