Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.

The relationship between amyloid and toxic species is a central problem since the discovery of amyloid structures in different diseases. Despite intensive efforts in the field, the deleterious species remains unknown at the molecular level. This may reflect the lack of any structure-toxicity study b...

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Autores principales:	Julien Couthouis, Karine Rébora, Françoise Immel, Karine Berthelot, Michel Castroviejo, Christophe Cullin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0efad63b73614770a7f2deee324e0620
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spelling	oai:doaj.org-article:0efad63b73614770a7f2deee324e06202021-11-25T06:16:56ZScreening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.1932-620310.1371/journal.pone.0004539https://doaj.org/article/0efad63b73614770a7f2deee324e06202009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19262694/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The relationship between amyloid and toxic species is a central problem since the discovery of amyloid structures in different diseases. Despite intensive efforts in the field, the deleterious species remains unknown at the molecular level. This may reflect the lack of any structure-toxicity study based on a genetic approach. Here we show that a structure-toxicity study without any biochemical prerequisite can be successfully achieved in yeast. A PCR mutagenesis of the amyloid domain of HET-s leads to the identification of a mutant that might impair cellular viability. Cellular and biochemical analyses demonstrate that this toxic mutant forms GFP-amyloid aggregates that differ from the wild-type aggregates in their shape, size and molecular organization. The chaperone Hsp104 that helps to disassemble protein aggregates is strictly required for the cellular toxicity. Our structure-toxicity study suggests that the smallest aggregates are the most toxic, and opens a new way to analyze the relationship between structure and toxicity of amyloid species.Julien CouthouisKarine RéboraFrançoise ImmelKarine BerthelotMichel CastroviejoChristophe CullinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 3, p e4539 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julien Couthouis Karine Rébora Françoise Immel Karine Berthelot Michel Castroviejo Christophe Cullin Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
description	The relationship between amyloid and toxic species is a central problem since the discovery of amyloid structures in different diseases. Despite intensive efforts in the field, the deleterious species remains unknown at the molecular level. This may reflect the lack of any structure-toxicity study based on a genetic approach. Here we show that a structure-toxicity study without any biochemical prerequisite can be successfully achieved in yeast. A PCR mutagenesis of the amyloid domain of HET-s leads to the identification of a mutant that might impair cellular viability. Cellular and biochemical analyses demonstrate that this toxic mutant forms GFP-amyloid aggregates that differ from the wild-type aggregates in their shape, size and molecular organization. The chaperone Hsp104 that helps to disassemble protein aggregates is strictly required for the cellular toxicity. Our structure-toxicity study suggests that the smallest aggregates are the most toxic, and opens a new way to analyze the relationship between structure and toxicity of amyloid species.
format	article
author	Julien Couthouis Karine Rébora Françoise Immel Karine Berthelot Michel Castroviejo Christophe Cullin
author_facet	Julien Couthouis Karine Rébora Françoise Immel Karine Berthelot Michel Castroviejo Christophe Cullin
author_sort	Julien Couthouis
title	Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
title_short	Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
title_full	Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
title_fullStr	Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
title_full_unstemmed	Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
title_sort	screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/0efad63b73614770a7f2deee324e0620
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Screening for toxic amyloid in yeast exemplifies the role of alternative pathway responsible for cytotoxicity.

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