Extra N-Terminal residues have a profound effect on the aggregation properties of the potential yeast prion protein Mca1

Erhardt, Marc; Wegrzyn, Renee D.; Deuerling, Elke

Extra N-Terminal residues have a profound effect on the aggregation properties of the potential yeast prion protein Mca1

Dateien

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Datum

2010

Autor:innen

Erhardt, Marc

Wegrzyn, Renee D.

Deuerling, Elke

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

PLoS ONE. 2010, 5(3), e9929. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0009929

Zusammenfassung

The metacaspase Mca1 from Saccharomyces cerevisiae displays a Q/N-rich region at its N-terminus reminiscent of yeast prion proteins. In this study, we show that the ability of Mca1 to form insoluble aggregates is modulated by a peptide stretch preceding its putative prion-forming domain. Based on its genomic locus, three potential translational start sites of Mca1 can give rise to two slightly different long Mca1 proteins or a short version, Mca1451/453 and Mca1432, respectively, although under normal physiological conditions Mca1432 is the predominant form expressed. All Mca1 variants exhibit the Q/N-rich regions, while only the long variants Mca1451/453 share an extra stretch of 19 amino acids at their N-terminal end. Strikingly, only long versions of Mca1 but not Mca1432 revealed pronounced aggregation in vivo and displayed prion-like properties when fused to the C-terminal domain of Sup35 suggesting that the N-terminal peptide element promotes the conformational switch of Mca1 protein into an insoluble state. Transfer of the 19 N-terminal amino acid stretch of Mca1451 to the N-terminus of firefly luciferase resulted in increased aggregation of luciferase, suggesting a protein destabilizing function of the peptide element. We conclude that the aggregation propensity of the potential yeast prion protein Mca1 in vivo is strongly accelerated by a short peptide segment preceding its Q/N-rich region and we speculate that such a conformational switch might occur in vivo via the usage of alternative translational start sites.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

ERHARDT, Marc, Renee D. WEGRZYN, Elke DEUERLING, 2010. Extra N-Terminal residues have a profound effect on the aggregation properties of the potential yeast prion protein Mca1. In: PLoS ONE. 2010, 5(3), e9929. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0009929

BibTex

@article{Erhardt2010Extra-12512,
  year={2010},
  doi={10.1371/journal.pone.0009929},
  title={Extra N-Terminal residues have a profound effect on the aggregation properties of the potential yeast prion protein Mca1},
  number={3},
  volume={5},
  journal={PLoS ONE},
  author={Erhardt, Marc and Wegrzyn, Renee D. and Deuerling, Elke},
  note={Article Number: e9929}
}

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    <dcterms:abstract xml:lang="eng">The metacaspase Mca1 from Saccharomyces cerevisiae displays a Q/N-rich region at its N-terminus reminiscent of yeast prion proteins. In this study, we show that the ability of Mca1 to form insoluble aggregates is modulated by a peptide stretch preceding its putative prion-forming domain. Based on its genomic locus, three potential translational start sites of Mca1 can give rise to two slightly different long Mca1 proteins or a short version, Mca1451/453 and Mca1432, respectively, although under normal physiological conditions Mca1432 is the predominant form expressed. All Mca1 variants exhibit the Q/N-rich regions, while only the long variants Mca1451/453 share an extra stretch of 19 amino acids at their N-terminal end. Strikingly, only long versions of Mca1 but not Mca1432 revealed pronounced aggregation in vivo and displayed prion-like properties when fused to the C-terminal domain of Sup35 suggesting that the N-terminal peptide element promotes the conformational switch of Mca1 protein into an insoluble state. Transfer of the 19 N-terminal amino acid stretch of Mca1451 to the N-terminus of firefly luciferase resulted in increased aggregation of luciferase, suggesting a protein destabilizing function of the peptide element. We conclude that the aggregation propensity of the potential yeast prion protein Mca1 in vivo is strongly accelerated by a short peptide segment preceding its Q/N-rich region and we speculate that such a conformational switch might occur in vivo via the usage of alternative translational start sites.</dcterms:abstract>
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Universitätsbibliographie

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