The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically.
Cdc37 associates with the heat-shock protein 90 (Hsp90) molecular chaperone as one of several auxiliary proteins that are collectively referred to as Hsp90 co-chaperones. Cdc37 has been proposed to be a specificity factor for Hsp90, directing it notably towards kinases. It is not known whether Cdc37 is essential for viability in the budding yeast Saccharomyces cerevisiae because of Hsp90-dependent or -independent functions or both. Sti1 and Cpr7 are non-essential Hsp90 co-chaperones that bind to a common surface on Hsp90 through tetratricopeptide repeats (TPR). We have found that Sti1 is specifically retained from yeast extracts by immobilized Cdc37. Similarly, the endogenous proteins are also found in a complex. Moreover, purified recombinant Sti1 and Cdc37 interact in the complete absence of Hsp90. Complexes between Cdc37 and Sti1 are not unique to this TPR protein since endogenous Cdc37 can be co-purified with exogenously expressed Cpr7 fused to glutathione-S-transferase. The heterogeneity of Cdc37 complexes, both with and without Hsp90, may expand the functional diversity of Cdc37. Here we show that the combination of cdc37 and sti1 mutations is synthetically lethal, suggesting that direct contacts between Cdc37 and Sti1 may at least contribute to vital functions in yeast.
Abbas-Terki
Toufik
T
Département de Biologie Cellulaire, Université de Genève, Switzerland.
Briand
Pierre-André
PA
Donzé
Olivier
O
Picard
Didier
D
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D029721:Drosophila Proteins; D004926:Escherichia coli / Q000235:genetics; D005816:Genetic Complementation Test; D005982:Glutathione Transferase; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008970:Molecular Weight; D019696:Peptidylprolyl Isomerase / Q000502:physiology; D011233:Precipitin Tests; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D000097322:Peptidyl-Prolyl Isomerase D
D001426:Bacterial Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D029721:Drosophila Proteins; D005982:Glutathione Transferase; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D019696:Peptidylprolyl Isomerase; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C513270:CDC37 protein, S cerevisiae; C000631445:CPR7 protein, S cerevisiae; D000097322:Peptidyl-Prolyl Isomerase D; C072838:Streptomyces trypsin inhibitor 1 protein, Streptomyces