Functional Analysis of the Yeast 40 kDa Cyclophilin Cyp40 and Its Role for Viability and Steroid Receptor Regulation
| Autor: | Didier Picard, Rainer Warth, Pierre-André Briand |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cytoplasm
Receptors Steroid Saccharomyces cerevisiae Proteins Isomerase activity Molecular Sequence Data Clinical Biochemistry Saccharomyces cerevisiae Biochemistry Chromatography Affinity Fungal Proteins Immunophilins Cyclosporin a Humans Amino Acid Sequence HSP90 Heat-Shock Proteins Cloning Molecular Molecular Biology Heat-Shock Proteins Cyclophilin Amino Acid Isomerases chemistry.chemical_classification Binding Sites Endodeoxyribonucleases Base Sequence biology Stereoisomerism Peptidylprolyl Isomerase beta-Galactosidase biology.organism_classification Hsp90 Recombinant Proteins Yeast Amino acid Cell biology Molecular Weight chemistry Cyclosporine biology.protein Carrier Proteins Immunosuppressive Agents |
| Zdroj: | Biological Chemistry. 378 |
| ISSN: | 1437-4315 1431-6730 |
| DOI: | 10.1515/bchm.1997.378.5.381 |
| Popis: | We have identified and characterized a homolog of the 40 kDa cyclophilins in the budding yeast Saccharomyces cerevisiae. At the amino acid level, this novel yeast cyclophilin, termed Cyp40, is 47% identical to human cyclophilin-40. Recombinant Cyp40 produced in bacteria has a peptidyl-prolyl cis-trans isomerase activity with a catalytic efficiency (k[cat]/K[m]) of 0.5 x 10(6)M(-1)s(-1), which can be inhibited by cyclosporin A with an IC50 value of 60nM. Using a polyclonal antibody against Cyp40 we have found that Cyp40 is predominantly cytoplasmic, and that its expression is induced 3-4-fold by heat shock. Moreover, Cyp40 can be coprecipitated from yeast extracts with the cytosolic molecular chaperone Hsp90. Surprisingly, a Cyp40-deficient yeast strain is fully viable at normal and elevated temperatures. Cyp40 is also dispensable for normal regulation of vertebrate steroid receptors in yeast. While other immunophilins could conceivably compensate a Cyp40 defect, our results are compatible with the notion that immunophilins may be fortuitous partners in the biochemically established steroid receptor-Hsp90 complex. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|