Chaperone Activity with a Redox Switch

Jakob, Ursula; Muse, Wilson B.; Eser, Markus; Bardwell, James C.A.

doi:10.1016/s0092-8674(00)80547-4

Cited by 483 publications

(491 citation statements)

References 35 publications

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“…Hsp33 in its inactive conformation has four reactive cysteine residues in the thiolate anion form that bind Zn 2+ . Under conditions of oxidative stress, the four thiolates form two intramolecular disulfide bonds which cause release of Zn, and subsequent dimerization of oxidized monomers, which effectuates full activation of Hsp33's function as a chaperone [147][148][149]. Similarly, mammalian Hsp25, 60, 70, and 90 also have redox active cysteine residues, and their oxidation has been linked to the modification of various chaperone functions in conditions of oxidative stress [150][151][152][153].…”

Section: Regulation Of Molecular Adaptors and Chaperonesmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

698

652

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Section: Regulation Of Molecular Adaptors and Chaperonesmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

698

652

View full text Add to dashboard Cite

“…Wild-type Hsp33, Hsp33 1-235 , Hsp33(F187W W212F) and Hsp33(W212F Y267W) were all purified in the absence of reducing agents as described for wild-type Hsp33 in ref. 8 . All reactions were carried out in 40 mM potassium phosphate buffer (pH 7.5) unless mentioned otherwise.…”

Section: Strains Plasmids and Proteinsmentioning

confidence: 99%

“…Activation of Hsp33's chaperone function requires the presence of reactive oxygen species such as H 2 O 2 and hydroxyl radicals 7 . These are sensed by the thiol-containing zinc center of Hsp33's C terminus 8 . When not under stress conditions, the four invariant cysteine residues of Hsp33, which are arranged in a 232-CXC-234 and 265-CXXC-268 motif, are reduced and coordinate one zinc ion 9,10 .…”

mentioning

confidence: 99%

The redox-switch domain of Hsp33 functions as dual stress sensor

Ilbert

Horst

Ahrens

et al. 2007

Nat Struct Mol Biol

Self Cite

168

207

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The redox-regulated chaperone Hsp33 is specifically activated upon exposure of cells to peroxide stress at elevated temperatures. Here we show that Hsp33 harbors two interdependent stress-sensing regions located in the C-terminal redox-switch domain of Hsp33: a zinc center sensing peroxide stress conditions and an adjacent linker region responding to unfolding conditions. Neither of these sensors works sufficiently in the absence of the other, making the simultaneous presence of both stress conditions a necessary requirement for Hsp33's full activation. Upon activation, Hsp33's redox-switch domain adopts a natively unfolded conformation, thereby exposing hydrophobic surfaces in its N-terminal substrate-binding domain. The specific activation of Hsp33 by the oxidative unfolding of its redox-switch domain makes this chaperone optimally suited to quickly respond to oxidative stress conditions that lead to protein unfolding.Reactive oxygen species develop as unavoidable consequences of aerobic life. Their oxidizing effects on most cellular macromolecules can be deleterious to cells and organisms 1 . Cells have developed effective antioxidant systems to counteract this hazard (for review, see ref. 2 ). Disruption of the fine balance between oxidants and antioxidants, however, leads to the accumulation of reactive oxygen species and to a condition termed oxidative stress 3 . Oxidative stress conditions have been shown to develop in, and may even cause, numerous physiological and pathological conditions, such as aging, heart disease, diabetes and neurodegenerative diseases 4 .

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“…In this assay, cyan and yellow-fluorescent proteins are bridged by part of a bacterial heat shock protein [29,60] which contains redox-sensitive cysteine thiols [61,62]. The thiol groups are reduced at normal conditions but upon oxidation, a disulfide bond is formed that changes the conformation of the hinge domain and separates the YFP and CFP.…”

Section: Measurement Of Cellular Rosmentioning

confidence: 99%

Reactive oxygen species and cellular oxygen sensing

Cash

Pan

Simon

2007

Free Radical Biology and Medicine

160

100

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Many organisms activate adaptive transcriptional programs to help them cope with decreased oxygen levels, or hypoxia, in their environment. These responses are triggered by various oxygen sensing systems in bacteria, yeast and metazoans. In metazoans, the hypoxia inducible factors (HIFs) mediate the adaptive transcriptional response to hypoxia by upregulating genes involved in maintaining bioenergetic homeostasis. The HIFs in turn are regulated by HIF-specific prolyl hydroxlase activity, which is sensitive to cellular oxygen levels and other factors such as tricarboxylic acid cycle metabolites and reactive oxygen species (ROS). Establishing a role for ROS in cellular oxygen sensing has been challenging since ROS are intrinsically unstable and difficult to measure. However, recent advances in fluorescence energy transfer resonance (FRET)-based methods for measuring ROS are alleviating some of the previous difficulties associated with dyes and luminescent chemicals. In addition, new genetic models have demonstrated that functional mitochondrial electron transport and associated ROS production during hypoxia are required for HIF stabilization in mammalian cells. Current efforts are directed at how ROS mediate prolyl hydroxylase activity and hypoxic HIF stabilization. Progress in understanding this process has been enhanced by the development of the FRET-based ROS probe, an vivo prolyl hydroxylase reporter and various genetic models harboring mutations in components of the mitochondrial electron transport chain.

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Chaperone Activity with a Redox Switch

Cited by 483 publications

References 35 publications

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

The redox-switch domain of Hsp33 functions as dual stress sensor

Reactive oxygen species and cellular oxygen sensing

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