TY - JOUR
T1 - Phase separation of a yeast prion protein promotes cellular fitness
AU - Franzmann, Titus M.
AU - Jahnel, Marcus
AU - Pozniakovsky, Andrei
AU - Mahamid, Julia
AU - Holehouse, Alex S.
AU - Nüske, Elisabeth
AU - Richter, Doris
AU - Baumeister, Wolfgang
AU - Grill, Stephan W.
AU - Pappu, Rohit V.
AU - Hyman, Anthony A.
AU - Alberti, Simon
N1 - Funding Information:
We thank the following Services and Facilities of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) for their support: We thank B. Borgonovo and R. Lemaitre (Protein Expression Purification and Characterization) for help with protein expression and purification; B. Nitzsche and B. Schroth-Diez (Light Microscopy Facility) for help with light microscopy; F. Friedrich for support with visualization (Media Technologies and Outreach); and C. Iserman for a yeast strain BY4742 coexpressing Sup35-GFP and Pab1-mCherry. We thank members of the MPI-CBG and C. Weber from the Max Planck Institute for the Physics of Complex systems for discussion and comments on the manuscript. R. Halfmann is acknowledged for providing the antibody against Sup35C domain. We gratefully acknowledge funding from the German Federal Ministry of Research and Education (BMBF 031A359A to T.M.F and A.A.H.). This work is supported by the MaxSynBio consortium, jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society. We further acknowledge the U.S. National Institutes of Health for grant 5RO1NS056114 to R.V.P., The Human Frontiers Program for grant RGP0034/2017 to S.A. and R.V.P, the Volkswagen “Life?” initiative for a grant to S.A., and the German Research Foundation (DFG) for a grant to S.A. All the data relevant to this study are included in the main paper or the supplementary materials.
PY - 2018/1/5
Y1 - 2018/1/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040130568&partnerID=8YFLogxK
U2 - 10.1126/science.aao5654
DO - 10.1126/science.aao5654
M3 - Article
C2 - 29301985
AN - SCOPUS:85040130568
SN - 0036-8075
VL - 359
JO - Science
JF - Science
IS - 6371
M1 - aao5654
ER -