title: Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation.
abstract: In higher eukaryotes, one of the two arginyl-tRNA synthetases (ArgRSs) has evolved to have an extended N-terminal domain that plays a crucial role in protein synthesis and cell growth and in integration into the multisynthetase complex (MSC). Here, we report a crystal structure of the MSC subcomplex comprising ArgRS, glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)/p43. In this complex, the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilized the N-terminal helix of ArgRS and abrogated its catalytic activity. Mutation of the N-terminal helix of ArgRS liberated GlnRS, which is known to control cell death. This ternary complex was further anchored to AIMP2/p38 through interaction with AIMP1. These findings demonstrate the importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex.
authors.affiliation: Department of Life Science and.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Life Science and.
authors.forename: Youngran
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang 790-784, South Korea;
authors.forename: Kyeong Sik
authors.initials: KS
authors.lastname: Jin
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea;
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea;
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Life Science and.
authors.forename: DongMing
authors.initials: D
authors.lastname: Wang
authors.affiliation: Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea;
authors.forename: Minyoung
authors.initials: M
authors.lastname: Park
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea;
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Jo
authors.affiliation: Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea;
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kwon
authors.affiliation: Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea;
authors.forename: Doyeun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea; and.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Korea University, Sejong 339-700, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jeon
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea; chahong@korea.ac.kr yunje@postech.ac.kr.
authors.forename: Kwang Yeon
authors.initials: KY
authors.lastname: Hwang
authors.affiliation: Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea;
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Life Science and chahong@korea.ac.kr yunje@postech.ac.kr.
authors.forename: Yunje
authors.initials: Y
authors.lastname: Cho
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D001126:Arginine-tRNA Ligase / Q000737:chemistry*; D001665:Binding Sites; D002850:Chromatography, Gel; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes; D016296:Mutagenesis; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry*; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry*; D012542:Scattering, Radiation
chemical_list: D016207:Cytokines; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D005982:Glutathione Transferase; D000604:Amino Acyl-tRNA Synthetases; C020659:glutaminyl-tRNA synthetase; D001126:Arginine-tRNA Ligase
keywords: AIMP1; arginyl-tRNA synthetase; crystal structure; glutaminyl-tRNA synthetase; multisynthetase complex