Influence of Hsp70 chaperone machinery on yeast prion propagation.

Chaperones have long been recognised for their essential roles in the cell. They are involved in the refolding or degradation of misfolded proteins as well as the correct folding of newly synthesised proteins. However recent experiments have discovered that chaperones also have an important role to play in the propagation and maintenance of prions in yeast. The following minireview focuses on the Hsp70 chaperone family and it's involvement in the propagation of yeast prions.

Importance of the Hsp70 ATPase domain in yeast prion propagation.

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.