NR ALAU
AU Sondheimer,N.; Lopez,N.; Craig,E.A.; Lindquist,S.L.
TI The role of Sis1 in the maintenance of the [RNQ+] prion
QU EMBO Journal 2001 May 15; 20(10): 2435-42
PT journal article
AB 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.
MH Fungal Proteins/*metabolism; Heat-Shock Proteins/genetics/*metabolism; Heat-Shock Proteins 70/metabolism; Luminescent Proteins/genetics/metabolism; Mutagenesis; Prions/genetics/*metabolism; Recombinant Fusion Proteins/genetics/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 S. Maryland Avenue MC1028, Chicago, IL 60637, USA
SP englisch
PO England