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The role of Sis1 in the maintenance of the [ RNQ + ] prion
Author(s) -
Sondheimer Neal,
Lopez Nelson,
Craig Elizabeth A.,
Lindquist Susan
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.10.2435
Subject(s) - biology , computational biology , virology
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.