Structures of translationally inactive mammalian ribosomes

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Cite this article as: eLife 2018;7:e40486 doi: 10.7554/eLife.40486

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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.

The following data sets were generated

1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9234).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9234
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9235).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9235
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9236).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9236
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9237).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9237
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9239).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9239
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9240).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9240
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9241).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9241
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the EMBL-EBI Protein Data Bank (accession no: EMD-9242).

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-9242
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the RCSB Protein Data Bank (accession no: 6MTB).

http://www.rcsb.org/pdb/explore/explore.do?structureId=6MTB
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the RCSB Protein Data Bank (accession no: 6MTC).

http://www.rcsb.org/pdb/explore/explore.do?structureId=6MTC
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the RCSB Protein Data Bank (accession no: 6MTD).

http://www.rcsb.org/pdb/explore/explore.do?structureId=6MTD
1. Brown A
2. Baird MR
3. Yip MCJ
4. Murray J
5. Shao S
(2018) Data from: Structures of translationally inactive mammalian ribosomes
Publicly available at the RCSB Protein Data Bank (accession no: 6MTE).

http://www.rcsb.org/pdb/explore/explore.do?structureId=6MTE

Article and author information

Author details

Alan Brown

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

For correspondence
alan_brown@hms.harvard.edu

Competing interests
The authors declare that no competing interests exist.
Matthew R Baird

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Matthew CJ Yip

Department of Cell Biology, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Jason Murray

Structural Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Sichen Shao

Department of Cell Biology, Harvard Medical School, Boston, United States

For correspondence
sichen_shao@hms.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2679-5537

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

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.