Journal article
Interaction of Heat Shock Protein 90 and the Co-chaperone Cpr6 with Ura2, a Bifunctional Enzyme Required for Pyrimidine Biosynthesis
The Journal of biological chemistry, Vol.288(38), pp.27406-27414
09/20/2013
Handle:
https://hdl.handle.net/2376/104190
PMCID: PMC3779735
PMID: 23926110
Abstract
Background:
Hsp90 and co-chaperones are critical for the folding and activation of client proteins.
Results:
Hsp90 and Cpr6, but not other tetratricopeptide repeat (TPR)-containing co-chaperones, interact with Ura2.
Conclusion:
The TPR domain of Cpr6 has unique functions, including interaction with Ura2, an enzyme required for pyrimidine biosynthesis.
Significance:
Identification of co-chaperone-specific interactions is crucial to understanding how to selectively target Hsp90 functions.
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.
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Details
- Title
- Interaction of Heat Shock Protein 90 and the Co-chaperone Cpr6 with Ura2, a Bifunctional Enzyme Required for Pyrimidine Biosynthesis
- Creators
- Abbey D Zuehlke - From the Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844Nicholas Wren - From the Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844Victoria Tenge - From the Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844Jill L Johnson - From the Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844
- Publication Details
- The Journal of biological chemistry, Vol.288(38), pp.27406-27414
- Academic Unit
- UNKNOWN
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Identifiers
- 99900546829401842
- Language
- English
- Resource Type
- Journal article