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Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216282/ https://www.ncbi.nlm.nih.gov/pubmed/34086935 http://dx.doi.org/10.1093/nar/gkab453 |
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author | Kim, Dong Kyu Lee, Hyun Joo Kong, Jiwon Cho, Ha Yeon Kim, Sunghoon Kang, Beom Sik |
author_facet | Kim, Dong Kyu Lee, Hyun Joo Kong, Jiwon Cho, Ha Yeon Kim, Sunghoon Kang, Beom Sik |
author_sort | Kim, Dong Kyu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8216282 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82162822021-06-22 Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes Kim, Dong Kyu Lee, Hyun Joo Kong, Jiwon Cho, Ha Yeon Kim, Sunghoon Kang, Beom Sik Nucleic Acids Res Structural Biology 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. Oxford University Press 2021-06-04 /pmc/articles/PMC8216282/ /pubmed/34086935 http://dx.doi.org/10.1093/nar/gkab453 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Kim, Dong Kyu Lee, Hyun Joo Kong, Jiwon Cho, Ha Yeon Kim, Sunghoon Kang, Beom Sik Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes |
title | Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes |
title_full | Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes |
title_fullStr | Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes |
title_full_unstemmed | Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes |
title_short | Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes |
title_sort | structural basis for the dynamics of human methionyl-trna synthetase in multi-trna synthetase complexes |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216282/ https://www.ncbi.nlm.nih.gov/pubmed/34086935 http://dx.doi.org/10.1093/nar/gkab453 |
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