Structures of translationally inactive mammalian ribosomes
- Harvard Medical School, United States
- MRC Laboratory of Molecular Biology, United Kingdom
Abstract
The cellular levels and activities of ribosomes directly regulate gene expression during numerous physiological processes. The mechanisms that globally repress translation are incompletely understood. Here, we use electron cryomicroscopy to analyze inactive ribosomes isolated from mammalian reticulocytes, the penultimate stage of red blood cell differentiation. We identify two types of ribosomes that are translationally repressed by protein interactions. The first comprises ribosomes sequestered with elongation factor 2 (eEF2) by SERPINE mRNA binding protein 1 (SERBP1) occupying the ribosomal mRNA entrance channel. The second type are translationally repressed by a novel ribosome-binding protein, interferon-related developmental regulator 2 (IFRD2), which spans the P and E sites and inserts a C-terminal helix into the mRNA exit channel to preclude translation. IFRD2 binds ribosomes with a tRNA occupying a noncanonical binding site, the 'Z site', on the ribosome. These structures provide functional insights into how ribosomal interactions may suppress translation to regulate gene expression.
Data availability
All cryo-EM maps and models have been deposited in EMDB under accession codes 9234, 9235, 9236, 9237, 9239, 9240, 9241 and 9242. All models have been deposited in PDB under accession codes 6MTB, 6MTC, 6MTD and 6MTE.
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9234).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9235).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9236).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9237).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9239).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9240).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9241).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9242).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the RCSB Protein Data Bank (accession no: 6MTB).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the RCSB Protein Data Bank (accession no: 6MTC).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the RCSB Protein Data Bank (accession no: 6MTD).
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Data from: Structures of translationally inactive mammalian ribosomesPublicly available at the RCSB Protein Data Bank (accession no: 6MTE).
Article and author information
Author details
Funding
Harvard Medical School (N/A)
- Alan Brown
- Matthew R Baird
- Matthew CJ Yip
- Sichen Shao
International Retinal Research Foundation (N/A)
- Alan Brown
E. Matilda Ziegler Foundation for the Blind (N/A)
- Alan Brown
Charles H. Hood Foundation (N/A)
- Sichen Shao
Richard and Susan Smith Family Foundation (N/A)
- Sichen Shao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nahum Sonenberg, McGill University, Canada
Publication history
- Received: July 26, 2018
- Accepted: October 12, 2018
- Accepted Manuscript published: October 24, 2018 (version 1)
- Version of Record published: November 9, 2018 (version 2)
Copyright
© 2018, Brown et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structures of translationally inactive mammalian ribosomes
eLife 7:e40486.
https://doi.org/10.7554/eLife.40486
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