Cargando…
Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis
EttA, energy-dependent translational throttle A, is a ribosomal factor that gates ribosome entry into the translation elongation cycle. A detailed understanding of its mechanism of action is limited due to the lack of high-resolution structures along its ATPase cycle. Here we present the cryo-electr...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782954/ https://www.ncbi.nlm.nih.gov/pubmed/35064151 http://dx.doi.org/10.1038/s41467-022-28078-1 |
_version_ | 1784638420626178048 |
---|---|
author | Cui, Zhicheng Li, Xiaojun Shin, Joonyoung Gamper, Howard Hou, Ya-Ming Sacchettini, James C. Zhang, Junjie |
author_facet | Cui, Zhicheng Li, Xiaojun Shin, Joonyoung Gamper, Howard Hou, Ya-Ming Sacchettini, James C. Zhang, Junjie |
author_sort | Cui, Zhicheng |
collection | PubMed |
description | EttA, energy-dependent translational throttle A, is a ribosomal factor that gates ribosome entry into the translation elongation cycle. A detailed understanding of its mechanism of action is limited due to the lack of high-resolution structures along its ATPase cycle. Here we present the cryo-electron microscopy (cryo-EM) structures of EttA from Mycobacterium tuberculosis (Mtb), referred to as MtbEttA, in complex with the Mtb 70S ribosome initiation complex (70SIC) at the pre-hydrolysis (ADPNP) and transition (ADP-VO(4)) states, and the crystal structure of MtbEttA alone in the post-hydrolysis (ADP) state. We observe that MtbEttA binds the E-site of the Mtb 70SIC, remodeling the P-site tRNA and the ribosomal intersubunit bridge B7a during the ribosomal ratcheting. In return, the rotation of the 30S causes conformational changes in MtbEttA, forcing the two nucleotide-binding sites (NBSs) to alternate to engage each ADPNP in the pre-hydrolysis states, followed by complete engagements of both ADP-VO(4) molecules in the ATP-hydrolysis transition states. In the post-hydrolysis state, the conserved ATP-hydrolysis motifs of MtbEttA dissociate from both ADP molecules, leaving two nucleotide-binding domains (NBDs) in an open conformation. These structures reveal a dynamic interplay between MtbEttA and the Mtb ribosome, providing insights into the mechanism of translational regulation by EttA-like proteins. |
format | Online Article Text |
id | pubmed-8782954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87829542022-02-04 Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis Cui, Zhicheng Li, Xiaojun Shin, Joonyoung Gamper, Howard Hou, Ya-Ming Sacchettini, James C. Zhang, Junjie Nat Commun Article EttA, energy-dependent translational throttle A, is a ribosomal factor that gates ribosome entry into the translation elongation cycle. A detailed understanding of its mechanism of action is limited due to the lack of high-resolution structures along its ATPase cycle. Here we present the cryo-electron microscopy (cryo-EM) structures of EttA from Mycobacterium tuberculosis (Mtb), referred to as MtbEttA, in complex with the Mtb 70S ribosome initiation complex (70SIC) at the pre-hydrolysis (ADPNP) and transition (ADP-VO(4)) states, and the crystal structure of MtbEttA alone in the post-hydrolysis (ADP) state. We observe that MtbEttA binds the E-site of the Mtb 70SIC, remodeling the P-site tRNA and the ribosomal intersubunit bridge B7a during the ribosomal ratcheting. In return, the rotation of the 30S causes conformational changes in MtbEttA, forcing the two nucleotide-binding sites (NBSs) to alternate to engage each ADPNP in the pre-hydrolysis states, followed by complete engagements of both ADP-VO(4) molecules in the ATP-hydrolysis transition states. In the post-hydrolysis state, the conserved ATP-hydrolysis motifs of MtbEttA dissociate from both ADP molecules, leaving two nucleotide-binding domains (NBDs) in an open conformation. These structures reveal a dynamic interplay between MtbEttA and the Mtb ribosome, providing insights into the mechanism of translational regulation by EttA-like proteins. Nature Publishing Group UK 2022-01-21 /pmc/articles/PMC8782954/ /pubmed/35064151 http://dx.doi.org/10.1038/s41467-022-28078-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Cui, Zhicheng Li, Xiaojun Shin, Joonyoung Gamper, Howard Hou, Ya-Ming Sacchettini, James C. Zhang, Junjie Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis |
title | Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis |
title_full | Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis |
title_fullStr | Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis |
title_full_unstemmed | Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis |
title_short | Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis |
title_sort | interplay between an atp-binding cassette f protein and the ribosome from mycobacterium tuberculosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782954/ https://www.ncbi.nlm.nih.gov/pubmed/35064151 http://dx.doi.org/10.1038/s41467-022-28078-1 |
work_keys_str_mv | AT cuizhicheng interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis AT lixiaojun interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis AT shinjoonyoung interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis AT gamperhoward interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis AT houyaming interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis AT sacchettinijamesc interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis AT zhangjunjie interplaybetweenanatpbindingcassettefproteinandtheribosomefrommycobacteriumtuberculosis |