The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90.
Ppt1 is the yeast member of a novel family of protein phosphatases, which is characterized by the presence of a tetratricopeptide repeat (TPR) domain. Ppt1 is known to bind to Hsp90, a molecular chaperone that performs essential functions in the folding and activation of a large number of client proteins. The function of Ppt1 in the Hsp90 chaperone cycle remained unknown. Here, we analyzed the function of Ppt1 in vivo and in vitro. We show that purified Ppt1 specifically dephosphorylates Hsp90. This activity requires Hsp90 to be directly attached to Ppt1 via its TPR domain. Deletion of the ppt1 gene leads to hyperphosphorylation of Hsp90 in vivo and an apparent decrease in the efficiency of the Hsp90 chaperone system. Interestingly, several Hsp90 client proteins were affected in a distinct manner. Our findings indicate that the Hsp90 multichaperone cycle is more complex than was previously thought. Besides its regulation via the Hsp90 ATPase activity and the sequential binding and release of cochaperones, with Ppt1, a specific phosphatase exists, which positively modulates the maturation of Hsp90 client proteins.
Wandinger
Sebastian K
SK
Department of Chemistry, Technische Universität München, Garching, Germany.
Suhre
Michael H
MH
Wegele
Harald
H
Buchner
Johannes
J
D002151:Calorimetry; D004926:Escherichia coli; D017353:Gene Deletion; D049452:Green Fluorescent Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D008156:Luciferases; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017510:Protein Folding; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013057:Spectrum Analysis
D018841:HSP90 Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008156:Luciferases; C089640:PPT1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases