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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 stress-dependent aggregation in yeast and age-dependent aggregation in C. elegans.Yeast proteins within our datasets were converted (if existent) to their orthologous C. elegans protein(s) and compared with the C. elegans proteins with a yeast orthologue from the 461 proteins isolated by32. 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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f8: Overlap between stress-dependent aggregation in yeast and age-dependent aggregation in C. elegans.Yeast proteins within our datasets were converted (if existent) to their orthologous C. elegans protein(s) and compared with the C. elegans proteins with a yeast orthologue from the 461 proteins isolated by32. Significance of the overlap was determined by a hypergeometric test and the fold difference over the expected overlap value is displayed.

Mentions: Finally, we wanted to compare our datasets with proteins that aggregate in another organism. A previous study identified 461 proteins in aged C. elegans protein aggregates32. Of these 461 proteins, 120 have a recognisable yeast orthologue which we used for comparative analysis with our datasets (referred to as CE-set). Within our protein aggregate datasets, we found that 126 (Unstressed-set), 30 (As-set), 25 (H2O2-set), 83 (AZC-set) and 84 (Common-set) proteins have recognisable C. elegans orthologues. Our analysis revealed a significant overlap between the yeast stress datasets (Common-set) and the CE-set. Overall, 69 (57.5%) of the proteins in our stress dataset are present in the CE-set (Fig. 8). 26 of the 126 orthologous proteins in the Unstressed-set overlap with the CE-set (22% of CE-set; 2.3 fold above the expected overlap; p = <0.001) (Fig. 8). Of the 26 overlapping proteins, 18 are ribosomal proteins and two are Hsp70 family chaperones. Significant overlaps are also found with the AZC- and Common-sets. Notable proteins, in which their presence in aggregates is conserved between our stress datasets and the CE-set, include components of the essential chaperonin Ctt ring complex. Subunits, Tcp1, Cct3, Cct4 and Cct8 are present in all our stress sets and have like-for-like orthologues in C .elegans, which are present in the CE-set. Another essential protein, Cdc48, is also conserved in all stress induced and CE-set aggregates. C. elegans has two orthologous of Cdc48 (cdc-48.1 and cdc-48.2), of which both forms are present in CE-set.


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

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

Overlap between stress-dependent aggregation in yeast and age-dependent aggregation in C. elegans.Yeast proteins within our datasets were converted (if existent) to their orthologous C. elegans protein(s) and compared with the C. elegans proteins with a yeast orthologue from the 461 proteins isolated by32. 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

f8: Overlap between stress-dependent aggregation in yeast and age-dependent aggregation in C. elegans.Yeast proteins within our datasets were converted (if existent) to their orthologous C. elegans protein(s) and compared with the C. elegans proteins with a yeast orthologue from the 461 proteins isolated by32. Significance of the overlap was determined by a hypergeometric test and the fold difference over the expected overlap value is displayed.
Mentions: Finally, we wanted to compare our datasets with proteins that aggregate in another organism. A previous study identified 461 proteins in aged C. elegans protein aggregates32. Of these 461 proteins, 120 have a recognisable yeast orthologue which we used for comparative analysis with our datasets (referred to as CE-set). Within our protein aggregate datasets, we found that 126 (Unstressed-set), 30 (As-set), 25 (H2O2-set), 83 (AZC-set) and 84 (Common-set) proteins have recognisable C. elegans orthologues. Our analysis revealed a significant overlap between the yeast stress datasets (Common-set) and the CE-set. Overall, 69 (57.5%) of the proteins in our stress dataset are present in the CE-set (Fig. 8). 26 of the 126 orthologous proteins in the Unstressed-set overlap with the CE-set (22% of CE-set; 2.3 fold above the expected overlap; p = <0.001) (Fig. 8). Of the 26 overlapping proteins, 18 are ribosomal proteins and two are Hsp70 family chaperones. Significant overlaps are also found with the AZC- and Common-sets. Notable proteins, in which their presence in aggregates is conserved between our stress datasets and the CE-set, include components of the essential chaperonin Ctt ring complex. Subunits, Tcp1, Cct3, Cct4 and Cct8 are present in all our stress sets and have like-for-like orthologues in C .elegans, which are present in the CE-set. Another essential protein, Cdc48, is also conserved in all stress induced and CE-set aggregates. C. elegans has two orthologous of Cdc48 (cdc-48.1 and cdc-48.2), of which both forms are present in CE-set.

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