title: Ion-specific effects on prion nucleation and strain formation.
abstract: Ordered, fibrous, self-seeding aggregates of misfolded proteins known as amyloids are associated with important diseases in mammals and control phenotypic traits in fungi. A given protein may adopt multiple amyloid conformations, known as variants or strains, each of which leads to a distinct disease pattern or phenotype. Here, we study the effect of Hofmeister ions on amyloid nucleation and strain generation by the prion domain-containing fragment (Sup35NM) of a yeast protein Sup35p. Strongly hydrated anions (kosmotropes) initiate nucleation quickly and cause rapid fiber elongation, whereas poorly hydrated anions (chaotropes) delay nucleation and mildly affect the elongation rate. For the first time, we demonstrate that kosmotropes favor formation of amyloid strains that are characterized by lower thermostability and higher frangibility in vitro and stronger phenotypic and proliferation patterns effectively in vivo as compared with amyloids formed in chaotropes. These phenomena point to inherent differences in the biochemistry of Hofmeister ions. Our work shows that the ionic composition of a solution not only influences the kinetics of amyloid nucleation but also determines the amyloid strain that is preferentially formed.
authors.affiliation: From the School of Chemical and Biomolecular Engineering,; Parker H. Petit Institute of Bioengineering and Bioscience.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rubin
authors.affiliation: Parker H. Petit Institute of Bioengineering and Bioscience,; School of Chemistry and Biochemistry, and.
authors.forename: Hasan
authors.initials: H
authors.lastname: Khosravi
authors.affiliation: Parker H. Petit Institute of Bioengineering and Bioscience,; School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Bruce
authors.affiliation: School of Chemistry and Biochemistry, and.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Lydon
authors.affiliation: From the School of Chemical and Biomolecular Engineering,; Parker H. Petit Institute of Bioengineering and Bioscience.
authors.forename: Sven H
authors.initials: SH
authors.lastname: Behrens
authors.affiliation: Parker H. Petit Institute of Bioengineering and Bioscience,; School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332. Electronic address: yury.chernoff@biology.gatech.edu.
authors.forename: Yury O
authors.initials: YO
authors.lastname: Chernoff
authors.affiliation: From the School of Chemical and Biomolecular Engineering,; Parker H. Petit Institute of Bioengineering and Bioscience,; School of Chemistry and Biochemistry, and. Electronic address: andreas.bommarius@chbe.gatech.edu.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Bommarius
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010454:Peptide Termination Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: Amyloid; Chaotrope; Hofmeister Series; Kosmotrope; Protein Aggregation; Protein Conformation; Translation Release Factors; Yeast