title: Distinct stress conditions result in aggregation of proteins with similar properties.
abstract: Protein aggregation is the abnormal association of proteins into larger aggregate structures which tend to be insoluble. This occurs during normal physiological conditions and in response to age or stress-induced protein misfolding and denaturation. In this present study we have defined the range of proteins that aggregate in yeast cells during normal growth and after exposure to stress conditions including an oxidative stress (hydrogen peroxide), a heavy metal stress (arsenite) and an amino acid analogue (azetidine-2-carboxylic acid). Our data indicate that these three stress conditions, which work by distinct mechanisms, promote the aggregation of similar types of proteins probably by lowering the threshold of protein aggregation. The proteins that aggregate during physiological conditions and stress share several features; however, stress conditions shift the criteria for protein aggregation propensity. This suggests that the proteins in aggregates are intrinsically aggregation-prone, rather than being proteins which are affected in a stress-specific manner. We additionally identified significant overlaps between stress aggregating yeast proteins and proteins that aggregate during ageing in yeast and C. elegans. We suggest that similar mechanisms may apply in disease- and non-disease settings and that the factors and components that control protein aggregation may be evolutionary conserved.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Weids
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ibstedt
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, S-405 30 Gothenburg, Sweden.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Tamás
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Grant
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D066329:Protein Aggregates; D015003:Yeasts / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D005656:Fungal Proteins; D066329:Protein Aggregates; D001383:Azetidinecarboxylic Acid