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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

Overlap between age-dependent and stress-dependent aggregation.Yeast proteins within our datasets were compared with proteins that were found to aggregate during postmitotic ageing in yeast31. Significance of the overlap was determined by a hypergeometric test and the fold difference over the expected overlap value is displayed.
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f7: Overlap between age-dependent and stress-dependent aggregation.Yeast proteins within our datasets were compared with proteins that were found to aggregate during postmitotic ageing in yeast31. Significance of the overlap was determined by a hypergeometric test and the fold difference over the expected overlap value is displayed.

Mentions: Protein aggregation is a hallmark of many ageing related diseases. A recent study identified 480 proteins that aggregate during postmitotic ageing in yeast31. When we compared these proteins with our datasets we found no significant overlap with our Unstressed-set. This makes sense given that our unstressed proteins were identified in exponential phase yeast cells rather than in an aged population. Interestingly, a significant overlap (1.4-fold, p = <0.001) was found between the ageing dataset and the Common-set, although there was no significant overlap for any single stress-specific condition (Fig. 7). Therefore, it appears that proteins which generally aggregate in response to stress are also likely to aggregate in aged yeast cells.


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

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

Overlap between age-dependent and stress-dependent aggregation.Yeast proteins within our datasets were compared with proteins that were found to aggregate during postmitotic ageing in yeast31. Significance of the overlap was determined by a hypergeometric test and the fold difference over the expected overlap value is displayed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Overlap between age-dependent and stress-dependent aggregation.Yeast proteins within our datasets were compared with proteins that were found to aggregate during postmitotic ageing in yeast31. Significance of the overlap was determined by a hypergeometric test and the fold difference over the expected overlap value is displayed.
Mentions: Protein aggregation is a hallmark of many ageing related diseases. A recent study identified 480 proteins that aggregate during postmitotic ageing in yeast31. When we compared these proteins with our datasets we found no significant overlap with our Unstressed-set. This makes sense given that our unstressed proteins were identified in exponential phase yeast cells rather than in an aged population. Interestingly, a significant overlap (1.4-fold, p = <0.001) was found between the ageing dataset and the Common-set, although there was no significant overlap for any single stress-specific condition (Fig. 7). Therefore, it appears that proteins which generally aggregate in response to stress are also likely to aggregate in aged yeast cells.

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