title: Yeast Short-Lived Actin-Associated Protein Forms a Metastable Prion in Response to Thermal Stress.
abstract: Self-perpetuating ordered protein aggregates (amyloids and prions) are associated with a variety of neurodegenerative disorders. Although environmental agents have been linked to certain amyloid diseases, the molecular basis of their action remains unclear. We have employed endogenous yeast prions as a model system to study environmental control of amyloid formation. A short-lived actin-associated yeast protein Lsb2 can trigger prion formation by other proteins in a mode regulated by the cytoskeleton and ubiquitin-dependent processes. Here, we show that such a heterologous prion induction is due to the ability of Lsb2 to form a transient prion state, generated in response to thermal stress. Evolutionary acquisition of prion-inducing activity by Lsb2 is traced to a single amino acid change, coinciding with the acquisition of thermotolerance in the Saccharomyces yeast lineage. This raises the intriguing possibility that the transient prion formation could aid in functioning of Lsb2 at higher temperatures.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: tcherno@emory.edu.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Chernova
authors.affiliation: School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-2000, USA; Laboratory of Amyloid Biology and Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Kiktev
authors.affiliation: School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-2000, USA.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Romanyuk
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Shanks
authors.affiliation: Division of Microbiology, Yerkes Research Center, Emory University, Atlanta, GA 30322, USA.
authors.forename: Oskar
authors.initials: O
authors.lastname: Laur
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Moiez
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Abheek
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Dami
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Maggie
authors.initials: M
authors.lastname: Mang
authors.affiliation: School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-2000, USA; Laboratory of Amyloid Biology and Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia. Electronic address: yury.chernoff@biology.gatech.edu.
authors.forename: Yury O
authors.initials: YO
authors.lastname: Chernoff
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: genekdw@emory.edu.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilkinson
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton; D008540:Meiosis; D018832:Molecular Chaperones / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010454:Peptide Termination Factors / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013696:Temperature; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; C583844:Lsb1 protein, S cerevisiae; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C568808:las17-binding protein Lsb2, S cerevisiae
keywords: Sup35; actin; amyloids; chaperone; environmental stress; heat shock; prions; ubiquitination