title: Contributions of the Prion Protein Sequence, Strain, and Environment to the Species Barrier.
abstract: Amyloid propagation requires high levels of sequence specificity so that only molecules with very high sequence identity can form cross-β-sheet structures of sufficient stringency for incorporation into the amyloid fibril. This sequence specificity presents a barrier to the transmission of prions between two species with divergent sequences, termed a species barrier. Here we study the relative effects of protein sequence, seed conformation, and environment on the species barrier strength and specificity for the yeast prion protein Sup35p from three closely related species of the Saccharomyces sensu stricto group; namely, Saccharomyces cerevisiae, Saccharomyces bayanus, and Saccharomyces paradoxus. Through in vivo plasmid shuffle experiments, we show that the major characteristics of the transmission barrier and conformational fidelity are determined by the protein sequence rather than by the cellular environment. In vitro data confirm that the kinetics and structural preferences of aggregation of the S. paradoxus and S. bayanus proteins are influenced by anions in accordance with their positions in the Hofmeister series, as observed previously for S. cerevisiae. However, the specificity of the species barrier is primarily affected by the sequence and the type of anion present during the formation of the initial seed, whereas anions present during the seeded aggregation process typically influence kinetics rather than the specificity of prion conversion. Therefore, our work shows that the protein sequence and the conformation variant (strain) of the prion seed are the primary determinants of cross-species prion specificity both in vivo and in vitro.
authors.affiliation: From the Schools of Chemical & Biomolecular Engineering and andreas.bommarius@chbe.gatech.edu.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Biology, Georgia Institute of Technology, Atlanta, Georgia 30332 and.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Bruce
authors.affiliation: Biology, Georgia Institute of Technology, Atlanta, Georgia 30332 and.
authors.forename: Buxin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Biology, Georgia Institute of Technology, Atlanta, Georgia 30332 and.
authors.forename: Stefka
authors.initials: S
authors.lastname: Gyoneva
authors.affiliation: From the Schools of Chemical & Biomolecular Engineering and.
authors.forename: Sven H
authors.initials: SH
authors.lastname: Behrens
authors.affiliation: From the Schools of Chemical & Biomolecular Engineering and andreas.bommarius@chbe.gatech.edu.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Bommarius
authors.affiliation: Biology, Georgia Institute of Technology, Atlanta, Georgia 30332 and the Laboratory of Amyloid Biology and Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia yury.chernoff@biology.gatech.edu.
authors.forename: Yury O
authors.identifier: http://orcid.org/0000-0002-8934-9051
authors.initials: YO
authors.lastname: Chernoff
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002712:Chlorides / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D058507:Host Specificity; D007700:Kinetics; D009154:Mutation; D010454:Peptide Termination Factors / Q000378:metabolism; D010472:Perchlorates / Q000737:chemistry; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D066329:Protein Aggregates; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012440:Saccharomyces / Q000145:classification / Q000254:growth & development / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D020539:Sequence Analysis, Protein; D013045:Species Specificity; D013431:Sulfates / Q000737:chemistry
chemical_list: D015415:Biomarkers; D002712:Chlorides; D005656:Fungal Proteins; D010454:Peptide Termination Factors; D010472:Perchlorates; D011328:Prions; D066329:Protein Aggregates; D011994:Recombinant Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013431:Sulfates; C459790:Sup35 protein, Candida albicans; C494474:perchlorate
keywords: Hofmeister series; amyloid; prion; protein conformation; protein evolution; species barrier; yeast