Structural insights into dynamics of the BMV TLS aminoacylation
Abstract Brome Mosaic Virus (BMV) utilizes a tRNA-like structure (TLS) within its 3’ untranslated region to mimic host tRNA functions, aiding aminoacylation and viral replication. This study explores the structural dynamics of BMV TLS interacting with tyrosyl-tRNA synthetase (TyrRS) during aminoacyl...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56612-4 |
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| author | Wen Yang Ran Yi Jing Yao Yongxiang Gao Shanshan Li Qingguo Gong Kaiming Zhang |
| author_facet | Wen Yang Ran Yi Jing Yao Yongxiang Gao Shanshan Li Qingguo Gong Kaiming Zhang |
| author_sort | Wen Yang |
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| description | Abstract Brome Mosaic Virus (BMV) utilizes a tRNA-like structure (TLS) within its 3’ untranslated region to mimic host tRNA functions, aiding aminoacylation and viral replication. This study explores the structural dynamics of BMV TLS interacting with tyrosyl-tRNA synthetase (TyrRS) during aminoacylation. Using cryo-EM, we capture multiple states of the TLS-TyrRS complex, including unbound TLS, pre-1a, post-1a, and catalysis states, with resolutions of 4.6 Å, 3.5 Å, 3.7 Å, and 3.85 Å, respectively. These structural comparisons indicate dynamic changes in both TLS and TyrRS. Upon binding, TLS undergoes dynamic rearrangements, particularly with helices B3 and E pivoting, mediated by the unpaired A36 residue, ensuring effective recognition by TyrRS. The dynamic changes also include a more compact arrangement in the catalytic center of TyrRS and the insertion of 3’ CCA end into the enzyme’s active site, facilitating two-steps aminoacylation. Enzymatic assays further demonstrated the functional importance of TLS-TyrRS interactions, with mutations in key residues significantly impacting aminoacylation efficiency. Furthermore, Electrophoretic Mobility Shift Assay (EMSA) demonstrated that BMV TLS binds elongation factors EF1α and EF2, suggesting a multifaceted strategy to exploit host translational machinery. These findings not only enhance our knowledge of virus-host interactions but also offer potential targets for antiviral drug development. |
| format | Article |
| id | doaj-art-aab11848752044dbbcee4e2e274c6cbb |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-aab11848752044dbbcee4e2e274c6cbb2025-02-09T12:44:30ZengNature PortfolioNature Communications2041-17232025-02-0116111310.1038/s41467-025-56612-4Structural insights into dynamics of the BMV TLS aminoacylationWen Yang0Ran Yi1Jing Yao2Yongxiang Gao3Shanshan Li4Qingguo Gong5Kaiming Zhang6Department of Clinical Laboratory, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan UniversityDepartment of Clinical Laboratory, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract Brome Mosaic Virus (BMV) utilizes a tRNA-like structure (TLS) within its 3’ untranslated region to mimic host tRNA functions, aiding aminoacylation and viral replication. This study explores the structural dynamics of BMV TLS interacting with tyrosyl-tRNA synthetase (TyrRS) during aminoacylation. Using cryo-EM, we capture multiple states of the TLS-TyrRS complex, including unbound TLS, pre-1a, post-1a, and catalysis states, with resolutions of 4.6 Å, 3.5 Å, 3.7 Å, and 3.85 Å, respectively. These structural comparisons indicate dynamic changes in both TLS and TyrRS. Upon binding, TLS undergoes dynamic rearrangements, particularly with helices B3 and E pivoting, mediated by the unpaired A36 residue, ensuring effective recognition by TyrRS. The dynamic changes also include a more compact arrangement in the catalytic center of TyrRS and the insertion of 3’ CCA end into the enzyme’s active site, facilitating two-steps aminoacylation. Enzymatic assays further demonstrated the functional importance of TLS-TyrRS interactions, with mutations in key residues significantly impacting aminoacylation efficiency. Furthermore, Electrophoretic Mobility Shift Assay (EMSA) demonstrated that BMV TLS binds elongation factors EF1α and EF2, suggesting a multifaceted strategy to exploit host translational machinery. These findings not only enhance our knowledge of virus-host interactions but also offer potential targets for antiviral drug development.https://doi.org/10.1038/s41467-025-56612-4 |
| spellingShingle | Wen Yang Ran Yi Jing Yao Yongxiang Gao Shanshan Li Qingguo Gong Kaiming Zhang Structural insights into dynamics of the BMV TLS aminoacylation Nature Communications |
| title | Structural insights into dynamics of the BMV TLS aminoacylation |
| title_full | Structural insights into dynamics of the BMV TLS aminoacylation |
| title_fullStr | Structural insights into dynamics of the BMV TLS aminoacylation |
| title_full_unstemmed | Structural insights into dynamics of the BMV TLS aminoacylation |
| title_short | Structural insights into dynamics of the BMV TLS aminoacylation |
| title_sort | structural insights into dynamics of the bmv tls aminoacylation |
| url | https://doi.org/10.1038/s41467-025-56612-4 |
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