Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.

Détails

ID Serval
serval:BIB_34969488FC80
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.
Périodique
Journal of Cell Science
Auteur(s)
Jacobson T., Navarrete C., Sharma S.K., Sideri T.C., Ibstedt S., Priya S., Grant C.M., Christen P., Goloubinoff P., Tamás M.J.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
125
Numéro
Pt 21
Pages
5073-5083
Langue
anglais
Résumé
Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.
Mots-clé
Arsenic toxicity, Protein aggregation, Protein degradation, Protein folding, Yeast
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2012 14:34
Dernière modification de la notice
20/08/2019 14:21
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