Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation
- Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15084-9. doi: 10.1073/pnas.1408836111.
- 1. Department of Life Science and.
- 2. Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang 790-784, South Korea;
- 3. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea;
- 4. 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;
- 5. Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea; and.
- 6. College of Pharmacy, Korea University, Sejong 339-700, South Korea.
- 7. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea; [email protected] [email protected].
- 8. Department of Life Science and [email protected] [email protected].
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.