Limits...
Distinct stress conditions result in aggregation of proteins with similar properties.

Weids AJ, Ibstedt S, Tamás MJ, Grant CM - Sci Rep (2016)

Bottom Line: Protein aggregation is the abnormal association of proteins into larger aggregate structures which tend to be insoluble.This suggests that the proteins in aggregates are intrinsically aggregation-prone, rather than being proteins which are affected in a stress-specific manner.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.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.

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.

No MeSH data available.


Related in: MedlinePlus

Proteins are vulnerable for aggregation during synthesis/folding.(a) Translation rate. Estimated translation rates27 per protein in each set is shown. (b) Co-translational folding. Bars indicate the proportion of proteins in each set that are co-translational substrates of Ssb228. (c) Chaperone interactions. The number of chaperone interactions per protein in each set is plotted. (d) Chaperone interactions. The proportion of proteins in each set with at least one chaperone interaction is plotted. (e) Interactions with Hsp70 chaperones. The proportion of proteins in each set that interact with a specific Hsp70 chaperone is plotted. Statistical analyses were performed as described in Methods, and *indicates a significant difference (p < 0.05) compared to the Unaggregated set.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4834537&req=5

f5: Proteins are vulnerable for aggregation during synthesis/folding.(a) Translation rate. Estimated translation rates27 per protein in each set is shown. (b) Co-translational folding. Bars indicate the proportion of proteins in each set that are co-translational substrates of Ssb228. (c) Chaperone interactions. The number of chaperone interactions per protein in each set is plotted. (d) Chaperone interactions. The proportion of proteins in each set with at least one chaperone interaction is plotted. (e) Interactions with Hsp70 chaperones. The proportion of proteins in each set that interact with a specific Hsp70 chaperone is plotted. Statistical analyses were performed as described in Methods, and *indicates a significant difference (p < 0.05) compared to the Unaggregated set.

Mentions: Given that the aggregated proteins identified under both non-stress and stress conditions are highly expressed and abundant, we compared their translation rates with unaggregated proteins. For this analysis we compared the aggregated proteins with a genome-wide estimate of translation rates27. Proteins that aggregate under unstressed conditions are significantly enriched for proteins which show high rates of mRNA translation compared with unaggregated proteins (Fig. 5a). Similarly, in agreement with their higher protein abundances and expression levels (Fig. 3a,b), translation rates are also significantly increased in the Common-set as well as the As- and AZC-specific sets (Fig. 5A). Nevertheless, these proteins have considerably lower translation rates compared with the proteins in the Unstressed-set (Fig. 5a). In contrast, translation rates are not increased for the H2O2-set despite their enrichment for higher abundance and expression proteins (Fig. 5a).


Distinct stress conditions result in aggregation of proteins with similar properties.

Weids AJ, Ibstedt S, Tamás MJ, Grant CM - Sci Rep (2016)

Proteins are vulnerable for aggregation during synthesis/folding.(a) Translation rate. Estimated translation rates27 per protein in each set is shown. (b) Co-translational folding. Bars indicate the proportion of proteins in each set that are co-translational substrates of Ssb228. (c) Chaperone interactions. The number of chaperone interactions per protein in each set is plotted. (d) Chaperone interactions. The proportion of proteins in each set with at least one chaperone interaction is plotted. (e) Interactions with Hsp70 chaperones. The proportion of proteins in each set that interact with a specific Hsp70 chaperone is plotted. Statistical analyses were performed as described in Methods, and *indicates a significant difference (p < 0.05) compared to the Unaggregated set.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834537&req=5

f5: Proteins are vulnerable for aggregation during synthesis/folding.(a) Translation rate. Estimated translation rates27 per protein in each set is shown. (b) Co-translational folding. Bars indicate the proportion of proteins in each set that are co-translational substrates of Ssb228. (c) Chaperone interactions. The number of chaperone interactions per protein in each set is plotted. (d) Chaperone interactions. The proportion of proteins in each set with at least one chaperone interaction is plotted. (e) Interactions with Hsp70 chaperones. The proportion of proteins in each set that interact with a specific Hsp70 chaperone is plotted. Statistical analyses were performed as described in Methods, and *indicates a significant difference (p < 0.05) compared to the Unaggregated set.
Mentions: Given that the aggregated proteins identified under both non-stress and stress conditions are highly expressed and abundant, we compared their translation rates with unaggregated proteins. For this analysis we compared the aggregated proteins with a genome-wide estimate of translation rates27. Proteins that aggregate under unstressed conditions are significantly enriched for proteins which show high rates of mRNA translation compared with unaggregated proteins (Fig. 5a). Similarly, in agreement with their higher protein abundances and expression levels (Fig. 3a,b), translation rates are also significantly increased in the Common-set as well as the As- and AZC-specific sets (Fig. 5A). Nevertheless, these proteins have considerably lower translation rates compared with the proteins in the Unstressed-set (Fig. 5a). In contrast, translation rates are not increased for the H2O2-set despite their enrichment for higher abundance and expression proteins (Fig. 5a).

Bottom Line: Protein aggregation is the abnormal association of proteins into larger aggregate structures which tend to be insoluble.This suggests that the proteins in aggregates are intrinsically aggregation-prone, rather than being proteins which are affected in a stress-specific manner.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.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.

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.

No MeSH data available.


Related in: MedlinePlus