Cpr6 and Cpr7, two closely related Hsp90-associated immunophilins from Saccharomyces cerevisiae, differ in their functional properties

Hsp90 is an abundant cytosolic molecular chaperone. It controls the folding of target proteins including steroid hormone receptors and kinases in comp lex with several partner proteins. Prominent members of this protein family are large peptidyl prolyl cis/trans isomerases (PPIases), which catalyze t he cis/trans isomerization of prolyl peptide bonds in proteins and possess chaperone activity. In Saccharomyces cerevisiae, two closely related large Hsp90-associated PPIases, Cpr6 and Cpr7, exist. We show here that these hom ologous proteins bind with comparable affinity to Hsp90 but exhibit signifi cant structural and functional differences. Cpr6 is more stable than Cpr7 a gainst thermal denaturation and displays an up to 100-fold higher PPIase ac tivity. In contrast, the chaperone activity of Cpr6 is much lower than that of Cpr7. Based on these results we suggest that the two immunophilins pet- form overlapping but not identical tasks in the Hsp90 chaperone cycle.