Dimer-Oligomer Interconversion of Wild-type and Mutant Rat 2-Cys Peroxiredoxin

Heme is a redox-reactive molecule with vital and complex roles in bacterial metabolism, survival, and virulence. However, few intracellular heme partners were identified to date and are not well conserved in bacteria. The opportunistic pathogen Streptococcus agalactiae (group B Streptococcus) is a heme auxotroph, which acquires exogenous heme to activate an aerobic respiratory chain. We identified the alkyl hydroperoxide reductase AhpC, a member of the highly conserved thiol-dependent 2-Cys peroxiredoxins, as a heme-binding protein.

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

The 2-Cys Peroxiredoxin Alkyl Hydroperoxide Reductase C Binds Heme and Participates in Its Intracellular Availability in Streptococcus agalactiae

Lechardeur

Fernandez²,

Robert³

et al. 2010

“…Both Cys 52 and Cys 173 are reactive cysteines in Prx I. Glutathionylation of these two cysteines will inhibit the peroxidase activity of Prx I. In addition, structural analysis of Prx from various species (36,37) (38) have reported that glutathionylation of plant 1-Cys Prx from Populus tremula, which exists in a very different structure with a subunit interface different from that reported for mammalian 2-Cys Prx (39), could induce the dissociation of this dimeric 1-Cys Prx.…”

mentioning

confidence: 99%

Deglutathionylation of 2-Cys Peroxiredoxin Is Specifically Catalyzed by Sulfiredoxin

Park

Mieyal

Rhee

et al. 2009

110

108

Reversible protein glutathionylation plays a key role in cellular regulation and cell signaling and protects protein thiols from hyperoxidation. Sulfiredoxin (Srx), an enzyme that catalyzes the reduction of Cys-sulfinic acid derivatives of 2-Cys peroxiredoxins (2-Cys Prxs), has been shown to catalyze the deglutathionylation of actin. We show that deglutathionylation of 2-Cys Prx, a family of peroxidases, is specifically catalyzed by Srx. Using the ubiquitously expressed member of 2-Cys Prx, Prx I, we revealed the following.

“…A large number of studies have demonstrated that the oxidation state of peroxidatic cysteine Cys P governs the quaternary structure of typical 2-Cys Prxs (1,28,48). However, protein self-polymerization is not coupled exclusively to redox transformations of cysteine residues because the composition of the surrounding solvent and post-translational modifications also condition the proportion of 2-Cys Prx allocated to different (error bars)) of three independent experiments illustrated in the top.…”

Section: Discussionmentioning

confidence: 99%

ATP and Mg2+ Promote the Reversible Oligomerization and Aggregation of Chloroplast 2-Cys Peroxiredoxin

Arán

Ferrero

Wolosiuk

et al. 2011

2-Cys peroxiredoxins (2-Cys Prxs) are ubiquitous peroxidases with important roles in cellular antioxidant defense and hydrogen peroxide-mediated signaling. Post-translational modifications of conserved cysteines cause the transition from low to high molecular weight oligomers, triggering the functional change from peroxidase to molecular chaperone. However, it remains unclear how non-covalent interactions of 2-Cys Prx with metabolites modulate the quaternary structure. Here, we disclose that ATP and Mg 2؉(ATP/Mg) promote the self-polymerization of chloroplast 2-Cys Prx (polypeptide 23.5 kDa) into soluble higher order assemblies (>2 MDa) that proceed to insoluble aggregates beyond 5 mM ATP. Remarkably, the withdrawal of ATP or Mg 2؉ brings soluble oligomers and insoluble aggregates back to the native conformation without compromising the associated functions. As confirmed by transmission electron microscopy, ATP/Mg drive the toroidlike decamers (diameter 13 nm) to the formation of large spherelike particles (diameter ϳ30 nm). Circular dichroism studies on ATP-labeled 2-Cys Prx reveal that ATP/Mg enhance the proportion of ␤-sheets with the concurrent decrease in the content of ␣-helices. In line with this observation, the formation of insoluble aggregates is strongly prevented by 2,2,2-trifluoroethanol, a cosolvent employed to induce ␣-helical conformations. We further find that the response of self-polymerization to ATP/Mg departs abruptly from that of the associated peroxidase and chaperone activities when two highly conserved residues, Arg 129 and Arg 152 , are mutated. Collectively, our data uncover that non-covalent interactions of ATP/Mg with 2-Cys Prx modulate dynamically the quaternary structure, thereby coupling the non-redox chemistry of cell energy with redox transformations at cysteine residues.