Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor
Abstract Many RNA viruses employ internal ribosome entry sites (IRESs) in their genomic RNA to commandeer the host’s translational machinery for replication. The IRES from encephalomyocarditis virus (EMCV) interacts with eukaryotic translation initiation factor 4 G (eIF4G), recruiting the ribosomal...
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Format: | Article |
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Nature Portfolio
2023-08-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-40582-6 |
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author | Shunsuke Imai Hiroshi Suzuki Yoshinori Fujiyoshi Ichio Shimada |
author_facet | Shunsuke Imai Hiroshi Suzuki Yoshinori Fujiyoshi Ichio Shimada |
author_sort | Shunsuke Imai |
collection | DOAJ |
description | Abstract Many RNA viruses employ internal ribosome entry sites (IRESs) in their genomic RNA to commandeer the host’s translational machinery for replication. The IRES from encephalomyocarditis virus (EMCV) interacts with eukaryotic translation initiation factor 4 G (eIF4G), recruiting the ribosomal subunit for translation. Here, we analyze the three-dimensional structure of the complex composed of EMCV IRES, the HEAT1 domain fragment of eIF4G, and eIF4A, by cryo-electron microscopy. Two distinct eIF4G-interacting domains on the IRES are identified, and complex formation changes the angle therebetween. Further, we explore the dynamics of these domains by using solution NMR spectroscopy, revealing conformational equilibria in the microsecond to millisecond timescale. In the lowly-populated conformations, the base-pairing register of one domain is shifted with the structural transition of the three-way junction, as in the complex structure. Our study provides insights into the viral RNA’s sophisticated strategy for optimal docking to hijack the host protein. |
first_indexed | 2024-03-10T17:35:35Z |
format | Article |
id | doaj.art-78178287e2944361b00c4f2ec6822014 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-10T17:35:35Z |
publishDate | 2023-08-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
spelling | doaj.art-78178287e2944361b00c4f2ec68220142023-11-20T09:51:30ZengNature PortfolioNature Communications2041-17232023-08-0114111410.1038/s41467-023-40582-6Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factorShunsuke Imai0Hiroshi Suzuki1Yoshinori Fujiyoshi2Ichio Shimada3RIKEN Center for Biosystems Dynamics ResearchCellular and Structural Physiology Laboratory (CeSPL), Tokyo Medical and Dental UniversityCellular and Structural Physiology Laboratory (CeSPL), Tokyo Medical and Dental UniversityRIKEN Center for Biosystems Dynamics ResearchAbstract Many RNA viruses employ internal ribosome entry sites (IRESs) in their genomic RNA to commandeer the host’s translational machinery for replication. The IRES from encephalomyocarditis virus (EMCV) interacts with eukaryotic translation initiation factor 4 G (eIF4G), recruiting the ribosomal subunit for translation. Here, we analyze the three-dimensional structure of the complex composed of EMCV IRES, the HEAT1 domain fragment of eIF4G, and eIF4A, by cryo-electron microscopy. Two distinct eIF4G-interacting domains on the IRES are identified, and complex formation changes the angle therebetween. Further, we explore the dynamics of these domains by using solution NMR spectroscopy, revealing conformational equilibria in the microsecond to millisecond timescale. In the lowly-populated conformations, the base-pairing register of one domain is shifted with the structural transition of the three-way junction, as in the complex structure. Our study provides insights into the viral RNA’s sophisticated strategy for optimal docking to hijack the host protein.https://doi.org/10.1038/s41467-023-40582-6 |
spellingShingle | Shunsuke Imai Hiroshi Suzuki Yoshinori Fujiyoshi Ichio Shimada Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor Nature Communications |
title | Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor |
title_full | Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor |
title_fullStr | Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor |
title_full_unstemmed | Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor |
title_short | Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor |
title_sort | dynamically regulated two site interaction of viral rna to capture host translation initiation factor |
url | https://doi.org/10.1038/s41467-023-40582-6 |
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