| Author | Morais, Mariana Abrahão Bueno de | pt_BR |
| Author | Giuseppe, Priscila Oliveira de | pt_BR |
| Author | Souza, Tatiana de Arruda Campos Brasil de | pt_BR |
| Author | Alegria, Thiago G. P. | pt_BR |
| Author | Oliveira, Marcos A. | pt_BR |
| Author | Soares Netto, Luis Eduardo | pt_BR |
| Author | Murakami, Mario Tyago | pt_BR |
| Access date | 2016-08-29T19:07:50Z | |
| Available date | 2016-08-29T19:07:50Z | |
| Document date | 2015 | |
| Citation | MORAIS, Mariana Abrahão Bueno de et al. How pH modulates the dimer-decamer interconversion of 2-Cys Peroxiredoxins from the Prx1 Subfamily. Journal of Biological Chemistry. v. 290, n. 13, p. 8582-8590, 27 Mar. 2015. | pt_BR |
| ISSN | 0021-9258 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/15508 | |
| Sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Grants 2010/51730-0, 2011/10248-4, and 2012/24134-3 | pt_BR |
| Sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | pt_BR |
| Sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | pt_BR |
| Language | eng | pt_BR |
| Rights | open access | pt_BR |
| Title | How pH modulates the dimer-decamer interconversion of 2-Cys peroxiredoxins from the Prx1 subfamily | en |
| Type | Article | pt_BR |
| DOI | 10.1074/jbc.M114.619205 | pt_BR |
| Abstract | 2-Cys peroxiredoxins belonging to the Prx1 subfamily are Cys-based peroxidases that control the intracellular levels of H₂O₂ and seem to assume a chaperone function under oxidative stress conditions. The regulation of their peroxidase activity as well as the observed functional switch from peroxidase to chaperone involves changes in their quaternary structure. Multiple factors can modulate the oligomeric transitions of 2-Cys peroxiredoxins such as redox state, post-translational modifications, and pH. However, the molecular basis for the pH influence on the oligomeric state of these enzymes is still elusive. Herein, we solved the crystal structure of a typical 2-Cys peroxiredoxin from Leishmania in the dimeric (pH 8.5) and decameric (pH 4.4) forms, showing that conformational changes in the catalytic loop are associated with the pH-induced decamerization. Mutagenesis and biophysical studies revealed that a highly conserved histidine (His¹¹³) functions as a pH sensor that, at acidic conditions, becomes protonated and forms an electrostatic pair with Asp⁷⁶ from the catalytic loop, triggering the decamerization. In these 2-Cys peroxiredoxins, decamer formation is important for the catalytic efficiency and has been associated with an enhanced sensitivity to oxidative inactivation by overoxidation of the peroxidatic cysteine. In eukaryotic cells, exposure to high levels of H₂O₂ can trigger intracellular pH variations, suggesting that pH changes might act cooperatively with H₂O₂ and other oligomerization-modulator factors to regulate the structure and function of typical 2-Cys peroxiredoxins in response to oxidative stress. | en |
| Affilliation | Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. | pt_BR |
| Affilliation | Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica e Engenharia de Proteínas. Curitiba, PR, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Biociências. Departamento de Genética e Biologia Evolutiva. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade Estadual Paulista Júlio de Mesquita Filho. Departamento de Biologia. São Vicente, SP, Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Instituto de Biociências. Departamento de Genética e Biologia Evolutiva. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brasil. | pt_BR |
| Subject | Conformational change | en |
| Subject | Crystal structure | en |
| Subject | Leishmania | en |
| Subject | Peroxiredoxin | en |
| Subject | pH regulation | en |
| e-ISSN | 1083-351X | pt_BR |
