Phase separation of a yeast prion protein promotes cellular fitness
Top Cited Papers
- 5 January 2018
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 359 (6371), 47-+
- https://doi.org/10.1126/science.aao5654
Abstract
Despite the important role of prion domains in neurodegenerative disease, their physiological function has remained enigmatic. Previous work with yeast prions has defined prion domains as sequences that form self-propagating aggregates. Here, we uncovered an unexpected function of the canonical yeast prion protein Sup35. In stressed conditions, Sup35 formed protective gels via pH-regulated liquid-like phase separation followed by gelation. Phase separation was mediated by the N-terminal prion domain and regulated by the adjacent pH sensor domain. Phase separation promoted yeast cell survival by rescuing the essential Sup35 translation factor from stress-induced damage. Thus, prion-like domains represent conserved environmental stress sensors that facilitate rapid adaptation in unstable environments by modifying protein phase behavior.Funding Information
- National Institutes of Health (5RO1NS056114)
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- BMBF MaxSynBio (031A359A)
This publication has 56 references indexed in Scilit:
- Suicidal [ PSI + ] is a lethal yeast prionProceedings of the National Academy of Sciences of the United States of America, 2011
- pHluorin2: an enhanced, ratiometric, pH-sensitive green florescent proteinAdvances in Bioscience and Biotechnology, 2011
- Prions, protein homeostasis, and phenotypic diversityTrends in Cell Biology, 2010
- Eukaryotic Stress Granules: The Ins and Outs of TranslationMolecular Cell, 2009
- A Systematic Survey Identifies Prions and Illuminates Sequence Features of Prionogenic ProteinsCell, 2009
- Screening for Amyloid Aggregation by Semi-Denaturing Detergent-Agarose Gel ElectrophoresisJournal of Visualized Experiments, 2008
- A suite of Gateway® cloning vectors for high‐throughput genetic analysis in Saccharomyces cerevisiaeYeast, 2007
- Stress and prions: Lessons from the yeast modelFEBS Letters, 2007
- Automated electron microscope tomography using robust prediction of specimen movementsJournal of Structural Biology, 2005
- IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy contentBioinformatics, 2005