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

作者：Fu Yaoyao; Kim Youngran; Jin Kyeong Sik; Kim Hyun Sook; Kim Jong Hyun; Wang DongMing; Park Minyoung; Jo Chang Hwa; Kwon Nam Hoon; Kim Doyeun; Kim Myung Hee; Jeon Young Ho; Hwang Kwang Yeon^*; Kim Sunghoon; Cho Yunje

来源：Proceedings of the National Academy of Sciences, 2014, 111(42): 15084-15089.

DOI：10.1073/pnas.1408836111

• arginyl-tRNA synthetase
• multisynthetase complex
• crystal structure
• AIMP1
• glutaminyl-tRNA synthetase

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.

• 出版日期2014-10-21