Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 25, Pages E3169-E3178Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1422594112
Keywords
signal recognition particle; trigger factor; ribosome; protein biogenesis; GTPases
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Funding
- National Institutes of Health (NIH) [GM078024]
- NIH NIGMS Ruth L. Kirschstein National Research Service Award [F31GM095294]
- Henry Dreyfus Teacher-Scholar Award
- Packard and Lucile Fellowship in science and engineering
- Gordon and Betty Moore Foundation [GBMF2939]
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The ribosome exit site is a crowded environment where numerous factors contact nascent polypeptides to influence their folding, localization, and quality control. Timely and accurate selection of nascent polypeptides into the correct pathway is essential for proper protein biogenesis. To understand how this is accomplished, we probe the mechanism by which nascent polypeptides are accurately sorted between the major cotranslational chaperone trigger factor (TF) and the essential cotranslational targeting machinery, signal recognition particle (SRP). We show that TF regulates SRP function at three distinct stages, including binding of the translating ribosome, membrane targeting via recruitment of the SRP receptor, and rejection of ribosome-bound nascent polypeptides beyond a critical length. Together, these mechanisms enhance the specificity of substrate selection into both pathways. Our results reveal a multilayered mechanism of molecular interplay at the ribosome exit site, and provide a conceptual framework to understand how proteins are selected among distinct biogenesis machineries in this crowded environment.
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