Interaction of Heat Shock Protein 90 and the Co-chaperone Cpr6 with Ura2, a Bifunctional Enzyme Required for Pyrimidine Biosynthesis

Zuehlke, Abbey D.; Wren, Nicholas; Tenge, Victoria R.; Johnson, Jill L.

doi:10.1074/jbc.m113.504142

Cited by 14 publications

(28 citation statements)

References 60 publications

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“…We previously demonstrated that isolation of Cpr6 results in copurification of Hsp90, Hsp70, and Ura2, an Hsp90 client protein required for pyrimidine biosynthesis (14). In this study, we found that isolation of Cpr6 also results in copurification of components of both the large and small ribosomal subunits.…”

supporting

confidence: 54%

“…We previously showed that purification of the Hsp90 cochaperone Cpr6 from yeast results in the copurification of Hsp90, Hsp70 (Ssa family), and the Hsp90 client Ura2 (14). Basic residues in the TPR domain of Cpr6 interact with carboxy-terminal EEVD residues of Hsp70 and/or Hsp90 in what has been termed a carboxylate clamp (23).…”

Section: Resultsmentioning

confidence: 99%

“…Wild-type (WT), ssz1, zuo1, egd1, egd2, and btt1 strains in the BY4741 background were also from Open Biosystems. Strains JJ762 (WT), JJ1138 (cpr6), JJ110 (cpr6 hsc82 hsp82/YEp24HSP82), JJ1093 (ura2), and JJ21 (cns1::TRP1/YCp50-CNS1), JJ1115 (cpr7), and JJ816 (hsc82 hsp82/YEp24HSP82), which are isogenic to W303, have been described previously (13,14,18,21).…”

Section: Methodsmentioning

confidence: 99%

“…pRS416GPDHis-Cpr6, pRS414GPDHis-Cpr6, pRS415 GPDHis-Sti1, pRS416GPDHis-Cpr7 (WT and Cpr7 193-393), pRS416 GPDHis-Cns1, YEP24-CNS1, and pRS317-CNS1 (WT and mutant) were previously described (13,14,18,22). Plasmids expressing untagged WT or mutant untagged Hsp90 (the Hsp82 isoform) (pRS314 HSP82 WT or ⌬MEEVD) were transformed into the indicated cpr6 hsc82 hsp82 strain harboring the YEp24-HSP82 plasmid.…”

Section: Methodsmentioning

confidence: 99%

“…Loss of CPR6 does not cause noticeable growth defects; loss of CPR7 results in slow, temperature-sensitive growth; and CNS1 is essential for viability (10)(11)(12). Cpr6 and Cpr7 share 38% amino acid identity yet exhibit different functions in vivo and in vitro (13)(14)(15)(16). In particular, overexpression of CPR7 rescues the temperature-sensitive defect of cns1-G90D (the G-to-D change at position 90 encoded by cns1) cells (17), while overexpression of CPR6 exacerbates the growth defects (18).…”

mentioning

confidence: 99%

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The Hsp90 Cochaperones Cpr6, Cpr7, and Cns1 Interact with the Intact Ribosome

et al. 2015

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The abundant molecular chaperone Hsp90 is essential for the folding and stabilization of hundreds of distinct client proteins. Hsp90 is assisted by multiple cochaperones that modulate Hsp90's ATPase activity and/or promote client interaction, but the in vivo functions of many of these cochaperones are largely unknown. We found that Cpr6, Cpr7, and Cns1 interact with the intact ribosome and that Saccharomyces cerevisiae lacking CPR7 or containing mutations in CNS1 exhibited sensitivity to the translation inhibitor hygromycin. Cpr6 contains a peptidyl-prolyl isomerase (PPIase) domain and a tetratricopeptide repeat (TPR) domain flanked by charged regions. Truncation or alteration of basic residues near the carboxy terminus of Cpr6 disrupted ribosome interaction. Cns1 contains an amino-terminal TPR domain and a poorly characterized carboxy-terminal domain. The isolated carboxy-terminal domain was able to interact with the ribosome. Although loss of CPR6 does not cause noticeable growth defects, overexpression of CPR6 results in enhanced growth defects in cells expressing the temperature-sensitive cns1-G90D mutation (the G-to-D change at position 90 encoded by cns1). Cpr6 mutants that exhibit reduced ribosome interaction failed to cause growth defects, indicating that ribosome interaction is required for in vivo functions of Cpr6. Together, these results represent a novel link between the Hsp90 molecular-chaperone machine and protein synthesis.

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supporting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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The Hsp90 Cochaperones Cpr6, Cpr7, and Cns1 Interact with the Intact Ribosome

et al. 2015

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Evidence for Hsp90 Co-chaperones in Regulating Hsp90 Function and Promoting Client Protein Folding

Cox

Johnson

2017

Methods in Molecular Biology

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Molecular chaperones are a diverse group of highly conserved proteins that transiently interact with partially folded polypeptide chains during normal cellular processes such as protein translation, translocation, and disassembly of protein complexes. Prior to folding or after denaturation, hydrophobic residues that are normally sequestered within a folded protein are exposed to the aqueous environment and are prone to aggregation or misfolding. Multiple classes of molecular chaperones, such as Hsp70s and Hsp40s, recognize and transiently bind polypeptides with exposed hydrophobic stretches in order to prevent misfolding. Other types of chaperones, such as Hsp90, have more specialized functions in that they appear to interact with only a subset of cellular proteins. This chapter focuses on the role of Hsp90 and partner co-chaperones in promoting the folding and activation of a diverse group of proteins with critical roles in cellular signaling and function.

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HSP70-HSP90 Chaperone Networking in Protein-Misfolding Disease

Prodromou

Aran-Guiu²,

Oberoi³

et al. 2022

Subcellular Biochemistry

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Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein folding, quality control and function. In particular, the heat shock protein (HSP) 70 and HSP90 molecular chaperone networks have been associated with neurodegenerative diseases caused by aberrant protein folding. The pathogenesis of these disorders usually includes the formation of deposits of misfolded, aggregated protein. HSP70 and HSP90, plus their co-chaperones, have been recognised as potent modulators of misfolded protein toxicity, inclusion formation and cell survival in cellular and animal models of neurodegenerative disease. Moreover, these chaperone machines function not only in folding, but also in proteasome mediated degradation of neurodegenerative disease proteins. This chapter gives an overview of the HSP70 and HSP90 chaperones, and their respective regulatory co-chaperones, and explores how the HSP70 and HSP90 chaperone systems form a larger functional network and its relevance to counteracting neurodegenerative disease associated with misfolded proteins and disruption of proteostasis.

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Interaction of Heat Shock Protein 90 and the Co-chaperone Cpr6 with Ura2, a Bifunctional Enzyme Required for Pyrimidine Biosynthesis

Cited by 14 publications

References 60 publications

The Hsp90 Cochaperones Cpr6, Cpr7, and Cns1 Interact with the Intact Ribosome

The Hsp90 Cochaperones Cpr6, Cpr7, and Cns1 Interact with the Intact Ribosome

Evidence for Hsp90 Co-chaperones in Regulating Hsp90 Function and Promoting Client Protein Folding

HSP70-HSP90 Chaperone Networking in Protein-Misfolding Disease

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