title: Prion propagation can occur in a prokaryote and requires the ClpB chaperone.
abstract: Prions are self-propagating protein aggregates that are characteristically transmissible. In mammals, the PrP protein can form a prion that causes the fatal transmissible spongiform encephalopathies. Prions have also been uncovered in fungi, where they act as heritable, protein-based genetic elements. We previously showed that the yeast prion protein Sup35 can access the prion conformation in Escherichia coli. Here, we demonstrate that E. coli can propagate the Sup35 prion under conditions that do not permit its de novo formation. Furthermore, we show that propagation requires the disaggregase activity of the ClpB chaperone. Prion propagation in yeast requires Hsp104 (a ClpB ortholog), and prior studies have come to conflicting conclusions about ClpB's ability to participate in this process. Our demonstration of ClpB-dependent prion propagation in E. coli suggests that the cytoplasmic milieu in general and a molecular machine in particular are poised to support protein-based heredity in the bacterial domain of life.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, United States Whitehead Institute for Biomedical Research, Cambridge, United States.
authors.forename: Andy H
authors.initials: AH
authors.lastname: Yuan
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, United States.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Garrity
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, United States.
authors.forename: Entela
authors.initials: E
authors.lastname: Nako
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, United States ahochschild@hms.harvard.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: Hochschild
mesh_terms: D049071:Endopeptidase Clp; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
chemical_list: D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C561470:New1 protein, S cerevisiae; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D012967:Sodium Dodecyl Sulfate; D049071:Endopeptidase Clp; C069775:ClpB protein, E coli
keywords: ClpB; Sup35; chaperones; prions; protein-based heredity