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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 Mg2+ (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 5mMATP. Remarkably, the withdrawal of ATP or Mg2+ 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 toroid-like decamers (diameter 13 nm) to the formation of large sphere-like particles (diameter ∼30 nm). Circular dichroism studies on ATP-labeled 2-Cys Prx reveal that ATP/Mg enhance the proportion of β-sheets with the concurrent decrease in the content of α-helices. In line with this observation, the formation of insoluble aggregates is strongly prevented by 2,2,2-trifluoroethanol, a cosolvent employed to induce α-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, Arg129 and Arg152, 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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Documento: Artículo
Título:ATP and Mg2+ promote the reversible oligomerization and aggregation of chloroplast 2-Cys peroxiredoxin
Autor:Aran, M.; Ferrero, D.; Wolosiuk, A.; Mora-García, S.; Wolosiuk, R.A.
Filiación:Instituto Leloir, Depto. Química Biológica-Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina
Gerencia Química, Comisión Nacional de Energía Atómica, Avda. Gral. Paz 1499, B1650KNA San Martín, Argentina
Centro Nacional de Biotecnología, 28049 Madrid, Spain
Palabras clave:2 ,2 ,2-trifluoroethanol; Antioxidant defense; Chaperone activity; Conserved residues; Cosolvents; Cysteine residues; Decamers; Functional changes; Helical conformation; Higher order; In-line; Low-to-high; Molecular chaperones; Native conformation; Non-covalent interaction; Peroxiredoxins; Post-translational modifications; Quaternary structure; Redox transformations; Self-polymerization; Amino acids; Chlorophyll; Conformations; Dichroism; Ethanol; Hydrogen peroxide; Oligomerization; Polymerization; Spheres; Transmission electron microscopy; Oligomers; 2 cysteine peroxiredoxin; adenosine triphosphate; arginine; cysteine; magnesium ion; peroxiredoxin; trifluoroethanol; unclassified drug; magnesium; peroxiredoxin; recombinant protein; vegetable protein; alpha helix; article; beta sheet; cell energy; chloroplast; circular dichroism; controlled study; enzyme activity; enzyme regulation; molecular interaction; molecular weight; nonhuman; oligomerization; oxidation reduction reaction; particle size; photochemistry; priority journal; protein aggregation; protein analysis; protein conformation; protein function; protein polymerization; protein processing; protein quaternary structure; rapeseed; surface plasmon resonance; transmission electron microscopy; chemistry; chloroplast; enzymology; genetics; metabolism; protein multimerization; protein secondary structure; Adenosine Triphosphate; Chloroplasts; Circular Dichroism; Magnesium; Peroxiredoxins; Plant Proteins; Protein Multimerization; Protein Structure, Quaternary; Protein Structure, Secondary; Recombinant Proteins
Página de inicio:23441
Página de fin:23451
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
CAS:adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; cysteine, 4371-52-2, 52-89-1, 52-90-4; magnesium ion, 22537-22-0; peroxiredoxin, 207137-51-7; trifluoroethanol, 75-89-8; magnesium, 7439-95-4; Adenosine Triphosphate, 56-65-5; Magnesium, 7439-95-4; Peroxiredoxins,; Plant Proteins; Recombinant Proteins


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---------- APA ----------
Aran, M., Ferrero, D., Wolosiuk, A., Mora-García, S. & Wolosiuk, R.A. (2011) . ATP and Mg2+ promote the reversible oligomerization and aggregation of chloroplast 2-Cys peroxiredoxin. Journal of Biological Chemistry, 286(26), 23441-23451.
---------- CHICAGO ----------
Aran, M., Ferrero, D., Wolosiuk, A., Mora-García, S., Wolosiuk, R.A. "ATP and Mg2+ promote the reversible oligomerization and aggregation of chloroplast 2-Cys peroxiredoxin" . Journal of Biological Chemistry 286, no. 26 (2011) : 23441-23451.
---------- MLA ----------
Aran, M., Ferrero, D., Wolosiuk, A., Mora-García, S., Wolosiuk, R.A. "ATP and Mg2+ promote the reversible oligomerization and aggregation of chloroplast 2-Cys peroxiredoxin" . Journal of Biological Chemistry, vol. 286, no. 26, 2011, pp. 23441-23451.
---------- VANCOUVER ----------
Aran, M., Ferrero, D., Wolosiuk, A., Mora-García, S., Wolosiuk, R.A. ATP and Mg2+ promote the reversible oligomerization and aggregation of chloroplast 2-Cys peroxiredoxin. J. Biol. Chem. 2011;286(26):23441-23451.