The shape of the ribosome exit tunnel affects cotranslational protein folding
- Stockholm University, Sweden
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States
- Stanford University, United States
Abstract
The E.coli ribosome exit tunnel can accommodate small folded proteins, while larger ones fold outside. It remains unclear, however, to what extent the geometry of the tunnel influences protein folding. Here, using E. coli ribosomes with deletions in loops in proteins uL23 and uL24 that protrude into the tunnel, we investigate how tunnel geometry determines where proteins of different sizes fold. We find that a 29-residue zinc-finger domain normally folding close to the uL23 loop folds deeper in the tunnel in uL23 Dloop ribosomes, while two ~100-residue protein normally folding close to the uL24 loop near the tunnel exit port fold at deeper locations in uL24 Dloop ribosomes, in good agreement with results obtained by coarse-grained molecular dynamics simulations. This supports the idea that cotranslational folding commences once a protein domain reaches a location in the exit tunnel where there is sufficient space to house the folded structure.
Data availability
Cryo-EM map deposited under accession code EMD-4319Atomic model for uL23 Dloop deposited under PDB accession number 6FU8
Article and author information
Author details
Harris D Bernstein
Funding
Knut och Alice Wallenbergs Stiftelse (2012.0282)
- Gunnar von Heijne
Vetenskapsrådet (621-2014-3713)
- Gunnar von Heijne
Cancerfonden (15 0888)
- Gunnar von Heijne
National Institutes of Health (Intramural)
- Robert Best
National Institutes of Health (Intramural)
- Harris D Bernstein
National Institutes of Health (R35GM122543)
- Fátima Pardo-Avila
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- John Kuriyan, University of California, Berkeley, United States
Version history
- Received: March 1, 2018
- Accepted: November 26, 2018
- Accepted Manuscript published: November 26, 2018 (version 1)
- Version of Record published: December 18, 2018 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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The shape of the ribosome exit tunnel affects cotranslational protein folding
eLife 7:e36326.
https://doi.org/10.7554/eLife.36326
