Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation

Yaoyao Fu, Youngran Kim, Kyeong Sik Jin, Hyun Sook Kim, Jong Hyun Kim, Dong Ming Wang, Minyoung Park, Chang Hwa Jo, Nam Hoon Kwon, Doyeun Kim, Myung Hee Kim, Young Ho Jeon, Kwang Yeon Hwang, Sunghoon Kim, Yunje Cho

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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.

Original languageEnglish
Pages (from-to)15084-15089
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number42
DOIs
Publication statusPublished - 2014 Oct 21

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Fu, Y., Kim, Y., Jin, K. S., Kim, H. S., Kim, J. H., Wang, D. M., Park, M., Jo, C. H., Kwon, N. H., Kim, D., Kim, M. H., Jeon, Y. H., Hwang, K. Y., Kim, S., & Cho, Y. (2014). Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation. Proceedings of the National Academy of Sciences of the United States of America, 111(42), 15084-15089. https://doi.org/10.1073/pnas.1408836111