Hsp90 chaperonins possess ATPase activity and bind heat shock transcription factors and peptidyl prolyl isomerases.

Nadeau, Kari; Das, Ananya; Walsh, Christopher T.

doi:10.1016/s0021-9258(18)54100-4

Cited by 229 publications

(21 citation statements)

References 44 publications

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“…The subject of the present study, CyP-A, binds to the heat shock protein hsp90 [15] and to the antioxidant protein Aop1 [16]. In addition the CyP-A-CSA complex binds strongly to calcineurin and inhibits its Ca# + -dependent protein phosphatase activity.…”

Section: Introductionmentioning

confidence: 87%

Evidence that cyclophilin-A protects cells against oxidative stress

Doyle

Virji

Crompton³

1999

Biochemical Journal

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Cyclophilin-A is the cytosolic isoform of a family of peptidylproline cis-trans-isomerases that bind cyclosporin A. This study investigates the role of cyclophilin-A in necrotic cell death, induced by 'chemical ischaemia' and by t-butylhydroperoxide. An 18-mer antisense phosphorothioate oligodeoxynucleotide was used to target a translated region of cyclophilin-A mRNA in rat neonatal cardiomyocytes. After a 24 h exposure to the oligonucleotide, the amount of cyclophilin-A in the cells was decreased by at least 93% as judged by immunological and enzymic criteria. For the enzyme assays, peptidyl proline cis-trans-isomerase activity was measured fluorimetrically in small (10 microl) volumes of cell extract. Immunoblots were developed with a polyclonal anti-cyclophilin-A antibody after sample isoelectric focusing and SDS/PAGE. Cyclophilin-A suppression had no effect on cyanide-plus-2-deoxyglucose-induced cell death. However, cyclophilin-A-suppressed cells were markedly more sensitive to t-butylhydroperoxide. Cyclosporin A conferred some resistance to the peroxide in both types of cell, but protection was greater in cyclophilin-A-suppressed cells, where cyclosporin A increased the survival time 2-fold. It is concluded that two cyclophilin isoforms are involved, in quite different ways, in peroxide-induced cell death. Cyclophilin-A has a protective role. Another isoform, possibly mitochondrial cyclophilin-D, has a deleterious role, such that blockade by cyclosporin A leads to protection.

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Section: Introductionmentioning

confidence: 87%

Evidence that cyclophilin-A protects cells against oxidative stress

Doyle

Virji

Crompton³

1999

Biochemical Journal

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“…Under proteotoxic stress conditions, misfolded proteins consume available chaperone capacity, thus reducing the pool of available chaperones to inhibit the HSR. Hsp90 (Nadeau et al, 1993;Ali et al, 1998;Zou et al, 1998), Hsp70 (Bonner et al, 2000;Zheng et al, 2016), and Hsp60 (Neef et al, 2014) have been reported to bind to Hsf1. This has led to speculation that loss of the chaperone-Hsf1 interaction is the regulatory step by which proteotoxic stressors activate the HSR.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Hsp90 availability reveals differential coupling to the heat shock response

Alford

Brandman

2018

Journal of Cell Biology

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“…Although Hsp90 holds a key role in protein quality control in healthy cells, Hsp90 is a central protein in the propagation of cancer, as it has been shown to chaperone oncoproteins. Eukaryotic Hsp90 also has at least 20 cochaperones which modulate its ATPase activity and bias the conformational dynamics of Hsp90 to stabilize individual conformational states [39][40][41][42][43][44]. In contrast, bacterial Hsp90 does not have any identified cochaperones that participate in protein remodeling.…”

Section: Introductionmentioning

confidence: 99%

Structural Communication between the E. coli Chaperones DnaK and Hsp90

Grindle

Carter

Alao

et al. 2021

IJMS

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The 70 kDa and 90 kDa heat shock proteins Hsp70 and Hsp90 are two abundant and highly conserved ATP-dependent molecular chaperones that participate in the maintenance of cellular homeostasis. In Escherichia coli, Hsp90 (Hsp90Ec) and Hsp70 (DnaK) directly interact and collaborate in protein remodeling. Previous work has produced a model of the direct interaction of both chaperones. The locations of the residues involved have been confirmed and the model has been validated. In this study, we investigate the allosteric communication between Hsp90Ec and DnaK and how the chaperones couple their conformational cycles. Using elastic network models (ENM), normal mode analysis (NMA), and a structural perturbation method (SPM) of asymmetric and symmetric DnaK-Hsp90Ec, we extract biologically relevant vibrations and identify residues involved in allosteric signaling. When one DnaK is bound, the dominant normal modes favor biological motions that orient a substrate protein bound to DnaK within the substrate/client binding site of Hsp90Ec and release the substrate from the DnaK substrate binding domain. The presence of one DnaK molecule stabilizes the entire Hsp90Ec protomer to which it is bound. Conversely, the symmetric model of DnaK binding results in steric clashes of DnaK molecules and suggests that the Hsp90Ec and DnaK chaperone cycles operate independently. Together, this data supports an asymmetric binding of DnaK to Hsp90Ec.

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Hsp90 chaperonins possess ATPase activity and bind heat shock transcription factors and peptidyl prolyl isomerases.

Cited by 229 publications

References 44 publications

Evidence that cyclophilin-A protects cells against oxidative stress

Evidence that cyclophilin-A protects cells against oxidative stress

Quantification of Hsp90 availability reveals differential coupling to the heat shock response

Structural Communication between the E. coli Chaperones DnaK and Hsp90

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