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 complex with several partner proteins. Prominent members of this protein family are large peptidyl prolyl cis/trans isomerases (PPIases), which catalyze the 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 homologous proteins bind with comparable affinity to Hsp90 but exhibit significant structural and functional differences. Cpr6 is more stable than Cpr7 against thermal denaturation and displays an up to 100-fold higher PPIase activity. In contrast, the chaperone activity of Cpr6 is much lower than that of Cpr7. Based on these results we suggest that the two immunophilins perform overlapping but not identical tasks in the Hsp90 chaperone cycle.
Mayr
C
C
Institut für Organische Chemie und Biochemie, Technische Universität München, 85747 Garching, Germany.
Richter
K
K
Lilie
H
H
Buchner
J
J
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002384:Catalysis; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D006163:Ribonuclease T1 / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D000097322:Peptidyl-Prolyl Isomerase D
D002352:Carrier Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D018841:HSP90 Heat-Shock Proteins; D019696:Peptidylprolyl Isomerase; D006163:Ribonuclease T1; C000631444:CPR6 protein, S cerevisiae; D000097322:Peptidyl-Prolyl Isomerase D; C000631445:CPR7 protein, S cerevisiae