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On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5)
It is now accepted that reactive oxygen species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS‐controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane‐bound enzyme...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317449/ https://www.ncbi.nlm.nih.gov/pubmed/31785178 http://dx.doi.org/10.1111/febs.15160 |
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author | Millana Fañanás, Elisa Todesca, Sofia Sicorello, Alessandro Masino, Laura Pompach, Petr Magnani, Francesca Pastore, Annalisa Mattevi, Andrea |
author_facet | Millana Fañanás, Elisa Todesca, Sofia Sicorello, Alessandro Masino, Laura Pompach, Petr Magnani, Francesca Pastore, Annalisa Mattevi, Andrea |
author_sort | Millana Fañanás, Elisa |
collection | PubMed |
description | It is now accepted that reactive oxygen species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS‐controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane‐bound enzymes (NOX1‐5 and DUOX1‐2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family member present in cyanobacteria, protists, plants, fungi, and the animal kingdom. We show that the calmodulin‐like regulatory EF‐domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C‐terminal lobe of the EF‐domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase (DH) domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the DH domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded‐to‐folded transition of the EF‐domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation. |
format | Online Article Text |
id | pubmed-7317449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73174492020-06-30 On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) Millana Fañanás, Elisa Todesca, Sofia Sicorello, Alessandro Masino, Laura Pompach, Petr Magnani, Francesca Pastore, Annalisa Mattevi, Andrea FEBS J Original Articles It is now accepted that reactive oxygen species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS‐controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane‐bound enzymes (NOX1‐5 and DUOX1‐2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family member present in cyanobacteria, protists, plants, fungi, and the animal kingdom. We show that the calmodulin‐like regulatory EF‐domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C‐terminal lobe of the EF‐domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase (DH) domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the DH domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded‐to‐folded transition of the EF‐domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation. John Wiley and Sons Inc. 2019-12-20 2020-06 /pmc/articles/PMC7317449/ /pubmed/31785178 http://dx.doi.org/10.1111/febs.15160 Text en © 2019 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Millana Fañanás, Elisa Todesca, Sofia Sicorello, Alessandro Masino, Laura Pompach, Petr Magnani, Francesca Pastore, Annalisa Mattevi, Andrea On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) |
title | On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) |
title_full | On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) |
title_fullStr | On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) |
title_full_unstemmed | On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) |
title_short | On the mechanism of calcium‐dependent activation of NADPH oxidase 5 (NOX5) |
title_sort | on the mechanism of calcium‐dependent activation of nadph oxidase 5 (nox5) |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317449/ https://www.ncbi.nlm.nih.gov/pubmed/31785178 http://dx.doi.org/10.1111/febs.15160 |
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