Overoxidation of 2-Cys Peroxiredoxin in Prokaryotes

Pascual, María Belén; Mata‐Cabana, Alejandro; Florencio, Francisco J.; Lindahl, Marika; Cejudo, Francisco Javier

doi:10.1074/jbc.m110.160465

Cited by 74 publications

(43 citation statements)

References 43 publications

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“…There are no reports indicating the involvement of the GGLG and/or YF motif for the Srx-Prx interaction. The GGLG and YF motifs were also identified in prokaryotic Prxs too [21]. The chaperone function is gained by formation of higher molecular weight complexes of Prx that looks like a stack or rings in transmission electron microscopy and X-ray crystallography studies [57].…”

Section: The Molecular Characteristics Of the Srx-prx Interaction Andmentioning

confidence: 99%

“…Depending on the levels of oxidative stress and amount of Prxs present in the system, the peroxidatic cysteine can be over-oxidized to sulfinic or sulfonic acid , leading to the loss of their antioxidant activity [20]. This hyperoxidation of Prx is present in majority of eukaryotes and few prokaryotes such as cyanobacteria [21]. It is important to clarify that in some older literature the hyperoxidation of Prx was reviewed as unique to eukaryotes.…”

Section: Introductionmentioning

confidence: 99%

“…It is important to clarify that in some older literature the hyperoxidation of Prx was reviewed as unique to eukaryotes. However, the latest research have indicated occurrence of Prx hyperoxidation in prokaryotes too [21]. The hyperoxidation of Prxs helps them to function as molecular chaperone, adding additional role in protein folding besides their function as antioxidants [22].…”

Section: Introductionmentioning

confidence: 99%

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The sulfiredoxin–peroxiredoxin (Srx–Prx) axis in cell signal transduction and cancer development

Mishra¹,

Jiang²,

Wu³

et al. 2015

Cancer Letters

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Redox signaling is a critical component of cell signaling pathways that is involved in regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Peroxiredoxin (Prx) is a family of thiol-based peroxidases that acts as a regulator of redox signaling. Members of Prx family can act as antioxidants and chaperone. Sulfiredoxin (Srx) is an antioxidant protein that exclusively reduces over-oxidized typical 2-Cys Prx. Srx have different affinities for individual Prx and it also catalyzes deglutathionylation of variety of substrates. Individual components of Srx-Prx system play critical roles in carcinogenesis by modulating cell signaling pathway involved in cell proliferation, migration and metastasis. Expression levels of individual components of Srx-Prx axis has been correlated with patient survival outcome in multiple cancer types. This review will summarize the molecular basis of differences in affinity of Srx for individual Prx and the role of individual components of Srx-Prx system in tumor progression and metastasis. This enhanced understanding of molecular aspects of Srx-Prx interaction and its role in cell signal transduction will help in defining Srx-Prx system as a future therapeutic target in human cancer.

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Section: The Molecular Characteristics Of the Srx-prx Interaction Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The sulfiredoxin–peroxiredoxin (Srx–Prx) axis in cell signal transduction and cancer development

Mishra¹,

Jiang²,

Wu³

et al. 2015

Cancer Letters

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“…The greater sensitivity of the eukaryotic over the prokaryotic Prxs is due to an extension at the C-terminus that restricts unfolding of the protein [21]. GGLG and YF motifs near the active site, as shown in Figure 2(A), are critical [19,22].…”

Section: Introductionmentioning

confidence: 99%

Kinetic analysis of structural influences on the susceptibility of peroxiredoxins 2 and 3 to hyperoxidation

Poynton

Peskin

Haynes

et al. 2016

Biochemical Journal

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Mammalian 2-cysteine peroxiredoxins (Prxs) are susceptible to hyperoxidation by excess H2O2. The cytoplasmic family member Prx2 hyperoxidizes more readily than mitochondrial Prx3 due to slower dimerization of the sulfenic acid (SpOH) intermediate. Four variant amino acids near the C-terminus have been shown to contribute to this difference. We have performed kinetic analysis of the relationship between hyperoxidation and disulfide formation, using whole-protein MS and comparing wild-type (WT) Prx2 and Prx3 with tail-swap mutants in which the four amino acids were reversed. These changes make Prx3 more sensitive and Prx2 less sensitive to hyperoxidation and accounted for ~70% of the difference between the two proteins. The tail swap mutant of Prx3 was also more susceptible when expressed in the mitochondria of HeLa cells. The hyperoxidized product at lower excesses of H2O2 was a semi-hyperoxidized dimer with one active site disulfide and the other a sulfinic acid. For Prx2, increasing the H2O2 concentration resulted in complete hyperoxidation. In contrast, only approximately half the Prx3 active sites underwent hyperoxidation and, even with high H2O2, the predominant product was the hyperoxidized dimer. Size exclusion chromatography (SEC) showed that the oligomeric forms of all redox states of Prx3 dissociated more readily into dimeric units than their Prx2 counterparts. Notably the species with one disulfide and one hyperoxidized active site was decameric for Prx2 and dimeric for Prx3. Reduction and re-oxidation of the hyperoxidized dimer of Prx3 produced hyperoxidized monomers, implying dissociation and rearrangement of the subunits of the functional homodimer.

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“…As Anabaena PCC7120 does not show good catalase activity [8,27], it is suggested that Prxs may be the principal components that detoxify H 2 O 2 in this organism. H 2 O 2 damages photosynthetic apparatus and severely affects F v /F m in several cyanobacteria [46].…”

Section: Discussionmentioning

confidence: 99%

Redox-dependent chaperone/peroxidase function of 2-Cys-Prx from the cyanobacterium Anabaena PCC7120: role in oxidative stress tolerance

2015

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BackgroundCyanobacteria, progenitors of plant chloroplasts, provide a suitable model system for plants to study adaptation towards different abiotic stresses. Genome of the filamentous, heterocystous, nitrogen-fixing cyanobacterium Anabaena PCC7120 harbours a single gene (alr4641) encoding a typical 2-Cys-Peroxiredoxins (2-Cys-Prxs). 2-Cys-Prxs are thiol-based peroxidases that also function as molecular chaperones in plants and other systems. The Alr4641 protein from Anabaena PCC7120 shows high level biochemical similarities with the plant 2-Cys-Prx. The physiological role played by the Alr4641 protein in Anabaena was addressed in this study.ResultsIn Anabaena PCC7120, alr4641 transcript /Alr4641 protein was induced in response to abiotic stresses and its promoter was active in the vegetative cells as well as heterocysts. The wild-type Alr4641 protein or Alr4641 lacking the peroxidatic cysteine (Alr4641C56S) or the resolving cysteine (Alr4641C178S) existed as higher oligomers in their native form. The wild-type or the mutant Alr4641 proteins showed similar chaperone activity, but only the wild-type protein exhibited peroxidase activity indicating that unlike peroxidase activity, chaperone activity was not dependent on cysteines. In contrast to other 2-Cys-Prxs, chaperone/peroxidase activity of Alr4641 was dependent on its redox state and not oligomerization status. Alr4641 could protect plasmid DNA from oxidative damage and physically associate with NADPH-dependent thioredoxin reductase (NTRC). Like 2-Cys-Prxs from plants (e.g. rice), Alr4641 could detoxify various peroxides using NTRC as reductant. On exposure to H2O2, recombinant Anabaena PCC7120 strain over-expressing Alr4641 (An4641+) showed reduced content of reactive oxygen species (ROS), intact photosynthetic functions and consequently better survival than the wild-type Anabaena PCC7120, indicating that Alr4641 can protect Anabaena from oxidative stress.ConclusionsThe peroxidase/chaperone function of Alr4641, its inherent transcriptional/translational induction under different abiotic stresses and localization in both vegetative cells and heterocysts could be an adaptive strategy to battle various oxidative stresses that Anabaena encounters during its growth. Moreover, the recombinant Anabaena strain over expressing Alr4641 showed higher resistance to oxidative stress, suggesting its potential to serve as stress-tolerant biofertilizers in rice fields.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-015-0444-2) contains supplementary material, which is available to authorized users.

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Overoxidation of 2-Cys Peroxiredoxin in Prokaryotes

Cited by 74 publications

References 43 publications

The sulfiredoxin–peroxiredoxin (Srx–Prx) axis in cell signal transduction and cancer development

The sulfiredoxin–peroxiredoxin (Srx–Prx) axis in cell signal transduction and cancer development

Kinetic analysis of structural influences on the susceptibility of peroxiredoxins 2 and 3 to hyperoxidation

Redox-dependent chaperone/peroxidase function of 2-Cys-Prx from the cyanobacterium Anabaena PCC7120: role in oxidative stress tolerance

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