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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

Proteins that aggregate during three distinct stress conditions in yeast.Number of proteins identified in aggregate fractions during As, AZC and H2O2 stress. For comparative analyses, the aggregated proteins were partitioned into non-overlapping datasets; 45 proteins uniquely identified in the As-set, 140 proteins within the AZC-set, 53 proteins within the H2O2-set, and a stress-set (Common-set) which contains 128 proteins that aggregate in at least two of the three stress conditions. The colours correspond to enrichment, taking the number of identifiable proteins into account.
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f1: Proteins that aggregate during three distinct stress conditions in yeast.Number of proteins identified in aggregate fractions during As, AZC and H2O2 stress. For comparative analyses, the aggregated proteins were partitioned into non-overlapping datasets; 45 proteins uniquely identified in the As-set, 140 proteins within the AZC-set, 53 proteins within the H2O2-set, and a stress-set (Common-set) which contains 128 proteins that aggregate in at least two of the three stress conditions. The colours correspond to enrichment, taking the number of identifiable proteins into account.

Mentions: To extend our previous analyses of protein aggregation1516, protein aggregates were isolated and identified following H2O2 and AZC stress. Insoluble protein aggregates were prepared as previously described2122 and identified using mass spectrometry following three independent experiments (see Materials and Methods). The H2O2-set and AZC-set were compared with our previously identified set of proteins which aggregate following arsenite stress (As-set)15. We noted that a considerable fraction of the proteins (~35%) aggregated in response to more than one stress condition (Fig. 1). Therefore, to facilitate a true comparative analysis of the stress-induced protein aggregates, we partitioned the identified proteins into non-overlapping datasets; 45 proteins uniquely identified in the As-set, 140 proteins within the AZC-set, 53 proteins within the H2O2-set, and a stress-set (Common-set) which contains 128 proteins that aggregate in at least two of the three stress conditions (Fig. 1).


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

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

Proteins that aggregate during three distinct stress conditions in yeast.Number of proteins identified in aggregate fractions during As, AZC and H2O2 stress. For comparative analyses, the aggregated proteins were partitioned into non-overlapping datasets; 45 proteins uniquely identified in the As-set, 140 proteins within the AZC-set, 53 proteins within the H2O2-set, and a stress-set (Common-set) which contains 128 proteins that aggregate in at least two of the three stress conditions. The colours correspond to enrichment, taking the number of identifiable proteins into account.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Proteins that aggregate during three distinct stress conditions in yeast.Number of proteins identified in aggregate fractions during As, AZC and H2O2 stress. For comparative analyses, the aggregated proteins were partitioned into non-overlapping datasets; 45 proteins uniquely identified in the As-set, 140 proteins within the AZC-set, 53 proteins within the H2O2-set, and a stress-set (Common-set) which contains 128 proteins that aggregate in at least two of the three stress conditions. The colours correspond to enrichment, taking the number of identifiable proteins into account.
Mentions: To extend our previous analyses of protein aggregation1516, protein aggregates were isolated and identified following H2O2 and AZC stress. Insoluble protein aggregates were prepared as previously described2122 and identified using mass spectrometry following three independent experiments (see Materials and Methods). The H2O2-set and AZC-set were compared with our previously identified set of proteins which aggregate following arsenite stress (As-set)15. We noted that a considerable fraction of the proteins (~35%) aggregated in response to more than one stress condition (Fig. 1). Therefore, to facilitate a true comparative analysis of the stress-induced protein aggregates, we partitioned the identified proteins into non-overlapping datasets; 45 proteins uniquely identified in the As-set, 140 proteins within the AZC-set, 53 proteins within the H2O2-set, and a stress-set (Common-set) which contains 128 proteins that aggregate in at least two of the three stress conditions (Fig. 1).

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