2. Academic Validation
  3. Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation

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.
Yaoyao Fu 1,  Youngran Kim 1,  Kyeong Sik Jin 2,  Hyun Sook Kim 3,  Jong Hyun Kim 4,  DongMing Wang 1,  Minyoung Park 4,  Chang Hwa Jo 3,  Nam Hoon Kwon 4,  Doyeun Kim 4,  Myung Hee Kim 5,  Young Ho Jeon 6,  Kwang Yeon Hwang 7,  Sunghoon Kim 4,  Yunje Cho 8
Affiliations

Affiliations

  • 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].
PMID: 25288775 DOI: 10.1073/pnas.1408836111
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.

Keywords

AIMP1; arginyl-tRNA synthetase; crystal structure; glutaminyl-tRNA synthetase; multisynthetase complex.

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