title: Driving amyloid toxicity in a yeast model by structural changes: a molecular approach.
abstract: The amyloid aggregation pathway is a multistep process, and many in vitro studies have highlighted the role of particular intermediates in the cellular toxicity of various amyloid diseases. In a previous study, we generated a yeast toxic mutant (M8) of the harmless model amyloid protein Het-s(218-289). In this study, we compared the aggregation characteristics of the wild-type (WT) and the toxic mutant at the molecular level. Both proteins formed fibrillar amyloid aggregates but with different dye-binding properties and X-ray diffraction patterns. The toxic amyloid formed very unusual short (80 nm) unbranched fibers visible on transmission electron microscopy. Fourier transform infrared spectroscopy demonstrated that M8 beta-sheets were essentially organized into a mixed parallel and antiparallel structure, whereas the WT protein displayed a predominantly parallel organization. Cellular toxicity may therefore be related to assembly of the toxic amyloid in a new aggregation pathway.
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, IBGC CNRS UMR 5095, Université Bordeaux 2 Victor Segalen, 1 rue Camille Saint Saëns, 33077 Bordeaux cedex, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Berthelot
authors.forename: Françoise
authors.initials: F
authors.lastname: Immel
authors.forename: Julie
authors.initials: J
authors.lastname: Géan
authors.forename: Sophie
authors.initials: S
authors.lastname: Lecomte
authors.forename: Reiko
authors.initials: R
authors.lastname: Oda
authors.forename: Brice
authors.initials: B
authors.lastname: Kauffmann
authors.forename: Christophe
authors.initials: C
authors.lastname: Cullin
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D000686:Amyloidosis; D009154:Mutation; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D015003:Yeasts
chemical_list: D000682:Amyloid