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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...

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Autores principales: Cui, Zhicheng, Li, Xiaojun, Shin, Joonyoung, Gamper, Howard, Hou, Ya-Ming, Sacchettini, James C., Zhang, Junjie
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
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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.
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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
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