NR AWWU
AU Loovers,H.M.; Guinan,E.; Jones,G.W.
TI Importance of the Hsp70 ATPase domain in yeast prion propagation
QU Genetics 2007 Feb; 175(2): 621-30
PT journal article; research support, non-u.s. gov't
AB The Saccharomyces cerevisiae non-Mendelian genetic element [PSI+] is the prion form of the translation termination factor Sup35p. The ability of [PSI+] to propagate efficiently has been shown previously to depend upon the action of protein chaperones. In this article we describe a genetic screen that identifies an array of mutants within the two major cytosolic Hsp70 chaperones of yeast, Ssa1p and Ssa2p, which impair the propagation of [PSI+]. All but one of the mutants was located within the ATPase domain of Hsp70, which highlights the important role of regulation of Hsp70-Ssa ATP hydrolysis in prion propagation. A subset of mutants is shown to alter Hsp70 function in a way that is distinct from that of previously characterized Hsp70 mutants that alter [PSI+] propagation and supports the importance of interdomain communication and Hsp70 interaction with nucleotide exchange factors in prion propagation. Analysis of the effects of Hsp70 mutants upon propagation of a second yeast prion [URE3] further classifies these mutants as having general or prion-specific inhibitory properties.
MH Adenosine Triphosphatases/*chemistry; Alleles; Fungal Proteins/*chemistry; HSP70 Heat-Shock Proteins/*chemistry; Heat-Shock Proteins/metabolism; Models, Biological; Mutation/genetics; Phenotype; Prions/*metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Saccharomyces cerevisiae/cytology/*metabolism; Saccharomyces cerevisiae Proteins/*chemistry/metabolism; Structure-Activity Relationship; Suppression, Genetic
AD Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland.
SP englisch
PO USA