Interaction of heat shock protein 90 and the co-chaperone Cpr6 with Ura2, a bifunctional enzyme required for pyrimidine biosynthesis.
The molecular chaperone heat shock protein 90 (Hsp90) is an essential protein required for the activity and stability of multiple proteins termed clients. Hsp90 cooperates with a set of co-chaperone proteins that modulate Hsp90 activity and/or target clients to Hsp90 for folding. Many of the Hsp90 co-chaperones, including Cpr6 and Cpr7, contain tetratricopeptide repeat (TPR) domains that bind a common acceptor site at the carboxyl terminus of Hsp90. We found that Cpr6 and Hsp90 interacted with Ura2, a protein critical for pyrimidine biosynthesis. Mutation or inhibition of Hsp90 resulted in decreased accumulation of Ura2, indicating it is an Hsp90 client. Cpr6 interacted with Ura2 in the absence of stable Cpr6-Hsp90 interaction, suggesting a direct interaction. However, loss of Cpr6 did not alter the Ura2-Hsp90 interaction or Ura2 accumulation. The TPR domain of Cpr6 was required for Ura2 interaction, but other TPR containing co-chaperones, including Cpr7, failed to interact with Ura2 or rescue CPR6-dependent growth defects. Further analysis suggests that the carboxyl-terminal 100 amino acids of Cpr6 and Cpr7 are critical for specifying their unique functions, providing new information about this important class of Hsp90 co-chaperones.
Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844.
Abbey D
AD
Zuehlke
Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844.
Nicholas
N
Wren
Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844.
Victoria
V
Tenge
Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844. Electronic address: jilljohn@uidaho.edu.
Jill L
JL
Johnson
D001221:Aspartate Carbamoyltransferase / Q000235:genetics / Q000378:metabolism*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics / Q000378:metabolism*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000097322:Peptidyl-Prolyl Isomerase D
D001221:Aspartate Carbamoyltransferase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D018841:HSP90 Heat-Shock Proteins; D011743:Pyrimidines; D029701:Saccharomyces cerevisiae Proteins; C000631444:CPR6 protein, S cerevisiae; D000097322:Peptidyl-Prolyl Isomerase D; C000631445:CPR7 protein, S cerevisiae; C110837:URA2 protein, S cerevisiae; C030986:pyrimidine
Hsp90; Molecular Chaperone; Protein-Protein Interactions; Pyrimidine; Yeast Genetics