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The role of Sis1 in the maintenance of the [RNQ(+)] prion

Yeast prions are inherited through proteins that exist in alternate, self-perpetuating conformational states. The mechanisms by which these states arise and are maintained are still poorly defined. Here we demonstrate for the first time that Sis1, a member of the Hsp40 chaperone family, plays a crit...

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Detalhes bibliográficos
Main Authors: Sondheimer, Neal, Lopez, Nelson, Craig, Elizabeth A., Lindquist, Susan
Formato: Artigo
Idioma:en
Publicado em: Oxford University Press 2001
Assuntos:
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC125465/
https://ncbi.nlm.nih.gov/pubmed/11350932
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/emboj/20.10.2435
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Resumo:Yeast prions are inherited through proteins that exist in alternate, self-perpetuating conformational states. The mechanisms by which these states arise and are maintained are still poorly defined. Here we demonstrate for the first time that Sis1, a member of the Hsp40 chaperone family, plays a critical role in the maintenance of a prion. The prion [RNQ(+)] is formed by Rnq1, which is present in the same physical complex as Sis1, but only when Rnq1 is in the prion state. The G/F domain of Sis1 is dispensable for rapid growth on rich medium, but is required for [RNQ(+)] maintenance, distinguishing essential regions of Sis1 from those needed for prion interaction. A specific Sis1 deletion mutant altered the physical aggregation pattern of Rnq1 without curing the prion. This variant state propagated in a heritable fashion after wild-type Sis1 function was restored, indicating that multiple physical states are compatible with prion maintenance and that changes in chaperone activity can create prion variants. Using a prion chimera we demonstrate that the prion-determinant domain of Rnq1 is genetically sufficient for control by Sis1.