Oligomerization dynamics and functionality of Trypanosoma cruzi cytosolic tryparedoxin peroxidase as peroxidase and molecular chaperone
- PMID: 31265897
- DOI: 10.1016/j.bbagen.2019.06.013
Oligomerization dynamics and functionality of Trypanosoma cruzi cytosolic tryparedoxin peroxidase as peroxidase and molecular chaperone
Abstract
Background: Trypanosoma cruzi cytosolic tryparedoxin peroxidase (c-TXNPx) is a 2-Cys peroxiredoxin that plays an important role in coping with host cell oxidative response during the infection process, for which it has been described as a virulence factor.
Methods: Four residues corresponding to c-TXNPx catalytic and solvent-exposed cysteines were individually mutated to serine by site-specific mutagenesis. Susceptibility to redox treatments and oligomeric dynamics were investigated by western-blot and gel filtration chromatography. Chaperone and peroxidase activities were determined.
Results: In this study we demonstrated that c-TXNPx exists as different oligomeric forms, from decameric to high molecular mass aggregates. Moreover, c-TXNPx functions as a dual-function protein acting both as a peroxidase and as a molecular chaperone. Its chaperone function was shown to be independent of the presence of catalytic cysteines, even in the reduced and decameric forms, although it is enhanced when the protein is overoxidized leading to the formation of high molecular mass aggregates.
Conclusions: c-TXNPx has chaperone activity which does not depend on the redox state. c-TXNPx does not undergo the dimer-decamer transition in the oxidized state described for other peroxiredoxins. Overoxidized c-TXNPx exists as different oligomeric forms from decamer to high molecular mass aggregates which are in a very slow dynamic equilibrium. The non-catalytic C57 residue may have a role in the maintenance of the decameric form, but seems not to have an alternative CP and CR role.
General significance: This study provides novel insights into some key aspects of the oligomerization dynamics and function of c-TXNPx.
Keywords: Chaperone; Hydrogen peroxide; Overoxidation; Peroxiredoxin; Trypanosoma cruzi.
Copyright © 2019. Published by Elsevier B.V.
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