Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes

Dong Kyu Kim, Hyun Joo Lee, Jiwon Kong, Ha Yeon Cho, Sunghoon Kim, Beom Sik Kang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


In mammals, eight aminoacyl-tRNA synthetases (AARSs) and three AARS-interacting multifunctional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC). MSC components possess extension peptides for MSC assembly and specific functions. Human cytosolic methionyl-tRNA synthetase (MRS) has appended peptides at both termini of the catalytic main body. The N-terminal extension includes a glutathione transferase (GST) domain responsible for interacting with AIMP3, and a long linker peptide between the GST and catalytic domains. Herein, we determined crystal structures of the human MRS catalytic main body, and the complex of the GST domain and AIMP3. The structures reveal human-specific structural details of the MRS, and provide a dynamic model for MRS at the level of domain orientation. A movement of zinc knuckles inserted in the catalytic domain is required for MRS catalytic activity. Depending on the position of the GST domain relative to the catalytic main body, MRS can either block or present its tRNA binding site. Since MRS is part of a huge MSC, we propose a dynamic switching between two possible MRS conformations; a closed conformation in which the catalytic domain is compactly attached to the MSC, and an open conformation with a free catalytic domain dissociated from other MSC components.

Original languageEnglish
Pages (from-to)6549-6568
Number of pages20
JournalNucleic acids research
Issue number11
Publication statusPublished - 2021 Jun 21

Bibliographical note

Funding Information:
National Research Foundation of Korea (NRF) [2015R1A4A1042271,2020R1A2C1003541]; Global Frontier Project [2014M3A6A4062857] funded by the Korean government (MSIT). Funding for open access charge: National Research Foundation of Korea (NRF) [2020R1A2C1003541].

Publisher Copyright:
© 2021 The Author(s).

All Science Journal Classification (ASJC) codes

  • Genetics


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