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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

Amino acid composition of aggregation-prone proteins.For each amino acid, the average percentage content was calculated from the proteins in each set and compared to the average amino acid content in the Unaggregated set. Red indicates a significant (p > 0.05) enrichment whereas green indicates a significant (p > 0.05) depletion compared to the Unaggregated set. Grey indicates no significant difference.
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f4: Amino acid composition of aggregation-prone proteins.For each amino acid, the average percentage content was calculated from the proteins in each set and compared to the average amino acid content in the Unaggregated set. Red indicates a significant (p > 0.05) enrichment whereas green indicates a significant (p > 0.05) depletion compared to the Unaggregated set. Grey indicates no significant difference.

Mentions: We next examined the relative amino acid content of the proteins enriched in our aggregate fractions. Proteins in the Unstressed-set are enriched in aliphatic amino acids including Ala, Gly and Val compared with the Unaggregated-set (Fig. 4), in agreement with their hydrophobic character (Fig. 3f). Furthermore, basic amino acids (Lys and Arg) are strongly enriched, whereas acidic amino acids (Asp, Glu) are underrepresented in the Unstressed-set (Fig. 4), which accounts for their higher pI compared with the Unaggregated-set (Fig. 3d). A number of amino acids are underrepresented in the Unstressed-set including Pro, Ser, His and sulphur-containing amino acids (Met, Cys) (Fig. 4). We also found that Gln and Asn are underrepresented in the Unstressed-set suggesting that the proteins in these aggregates are distinct from the well-known amyloid forming proteins. These amino acids are normally thought to underlie amyloid formation and have been linked to prion formation in yeast and mammalian neurological disorders including Huntington’s disease26.


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

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

Amino acid composition of aggregation-prone proteins.For each amino acid, the average percentage content was calculated from the proteins in each set and compared to the average amino acid content in the Unaggregated set. Red indicates a significant (p > 0.05) enrichment whereas green indicates a significant (p > 0.05) depletion compared to the Unaggregated set. Grey indicates no significant difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Amino acid composition of aggregation-prone proteins.For each amino acid, the average percentage content was calculated from the proteins in each set and compared to the average amino acid content in the Unaggregated set. Red indicates a significant (p > 0.05) enrichment whereas green indicates a significant (p > 0.05) depletion compared to the Unaggregated set. Grey indicates no significant difference.
Mentions: We next examined the relative amino acid content of the proteins enriched in our aggregate fractions. Proteins in the Unstressed-set are enriched in aliphatic amino acids including Ala, Gly and Val compared with the Unaggregated-set (Fig. 4), in agreement with their hydrophobic character (Fig. 3f). Furthermore, basic amino acids (Lys and Arg) are strongly enriched, whereas acidic amino acids (Asp, Glu) are underrepresented in the Unstressed-set (Fig. 4), which accounts for their higher pI compared with the Unaggregated-set (Fig. 3d). A number of amino acids are underrepresented in the Unstressed-set including Pro, Ser, His and sulphur-containing amino acids (Met, Cys) (Fig. 4). We also found that Gln and Asn are underrepresented in the Unstressed-set suggesting that the proteins in these aggregates are distinct from the well-known amyloid forming proteins. These amino acids are normally thought to underlie amyloid formation and have been linked to prion formation in yeast and mammalian neurological disorders including Huntington’s disease26.

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