title: The peptidyl-prolyl isomerase domain of the CyP-40 cyclophilin homolog Cpr7 is not required to support growth or glucocorticoid receptor activity in Saccharomyces cerevisiae.
abstract: CyP-40 cyclophilins are found in association with molecular chaperone Hsp90.steroid receptor complexes. The amino-terminal portion of these cyclophilins harbors the characteristic peptidyl-prolyl isomerase (PPIase) domain, whereas three copies of the tetratricopeptide (TPR) motif, a structure shown to be involved in protein-protein interactions, and a putative calmodulin-binding domain are located in the carboxyl-terminal half of the protein. The TPR domains mediate binding to Hsp90, but a requirement for the PPIase domain has not been established. To address this, we have investigated the effects of mutations that alter the PPIase domain of the Saccharomyces cerevisiae CyP-40 homolog, Cpr7. Because Cpr7 is required for rapid growth and full Hsp90 activity, a functional assessment of the PPIase domain could be performed in vivo. A mutation in the catalytic domain altering a conserved site predicted to be essential for isomerase activity did not compromise Cpr7 function. Furthermore, deletion of the entire PPIase domain did not significantly affect growth or Hsp90-mediated steroid receptor activity. These results indicate that the TPR-containing carboxyl terminus of Cpr7 is sufficient for fundamental Cpr7-dependent activity.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Duina
authors.forename: J A
authors.initials: JA
authors.lastname: Marsh
authors.forename: R B
authors.initials: RB
authors.lastname: Kurtz
authors.forename: H C
authors.initials: HC
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: Lindquist
authors.forename: R F
authors.initials: RF
authors.lastname: Gaber
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism; D013379:Substrate Specificity; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D002352:Carrier Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D018841:HSP90 Heat-Shock Proteins; D015688:Oncogene Protein pp60(v-src); D019696:Peptidylprolyl Isomerase; D011965:Receptors, Glucocorticoid; C000631445:CPR7 protein, S cerevisiae; D000097322:Peptidyl-Prolyl Isomerase D