title: Prion-inducing domain 2-114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments.
abstract: The yeast non-Mendelian genetic factor [PSI], which enhances the efficiency of tRNA-mediated nonsense suppression in Saccharomyces cerevisiae, is thought to be an abnormal cellular isoform of the Sup35 protein. Genetic studies have established that the N-terminal part of the Sup35 protein is sufficient for the genesis as well as the maintenance of [PSI]. Here we demonstrate that the N-terminal polypeptide fragment consisting of residues 2-114 of Sup35p, Sup35pN, spontaneously aggregates to form thin filaments in vitro. The filaments show a beta-sheet-type circular dichroism spectrum, exhibit increased protease resistance, and show amyloid-like optical properties. It is further shown that filament growth in freshly prepared Sup35pN solutions can be induced by seeding with a dilute suspension of preformed filaments. These results suggest that the abnormal cellular isoform of Sup35p is an amyloid-like aggregate and further indicate that seeding might be responsible for the maintenance of the [PSI] element in vivo.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, CH-8093 Zürich, Switzerland.
authors.forename: C Y
authors.initials: CY
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Tittmann
authors.forename: H
authors.initials: H
authors.lastname: Gross
authors.forename: R
authors.initials: R
authors.lastname: Gebert
authors.forename: M
authors.initials: M
authors.lastname: Aebi
authors.forename: K
authors.initials: K
authors.lastname: Wüthrich
mesh_terms: D000682:Amyloid / Q000648:ultrastructure*; D005656:Fungal Proteins / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D010446:Peptide Fragments / Q000737:chemistry; D010454:Peptide Termination Factors; D011328:Prions / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; D010446:Peptide Fragments; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins