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Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR
Bacillus subtilis encodes redox-sensing MarR-type regulators of the OhrR and DUF24-families that sense organic hydroperoxides, diamide, quinones or aldehydes via thiol-based redox-switches. In this article, we characterize the novel redox-sensing MarR/DUF24-family regulator HypR (YybR) that is activ...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351151/ https://www.ncbi.nlm.nih.gov/pubmed/22238377 http://dx.doi.org/10.1093/nar/gkr1316 |
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author | Palm, Gottfried J. Khanh Chi, Bui Waack, Paul Gronau, Katrin Becher, Dörte Albrecht, Dirk Hinrichs, Winfried Read, Randy J. Antelmann, Haike |
author_facet | Palm, Gottfried J. Khanh Chi, Bui Waack, Paul Gronau, Katrin Becher, Dörte Albrecht, Dirk Hinrichs, Winfried Read, Randy J. Antelmann, Haike |
author_sort | Palm, Gottfried J. |
collection | PubMed |
description | Bacillus subtilis encodes redox-sensing MarR-type regulators of the OhrR and DUF24-families that sense organic hydroperoxides, diamide, quinones or aldehydes via thiol-based redox-switches. In this article, we characterize the novel redox-sensing MarR/DUF24-family regulator HypR (YybR) that is activated by disulphide stress caused by diamide and NaOCl in B. subtilis. HypR controls positively a flavin oxidoreductase HypO that confers protection against NaOCl stress. The conserved N-terminal Cys14 residue of HypR has a lower pK(a) of 6.36 and is essential for activation of hypO transcription by disulphide stress. HypR resembles a 2-Cys-type regulator that is activated by Cys14–Cys49′ intersubunit disulphide formation. The crystal structures of reduced and oxidized HypR proteins were resolved revealing structural changes of HypR upon oxidation. In reduced HypR a hydrogen-bonding network stabilizes the reactive Cys14 thiolate that is 8–9 Å apart from Cys49′. HypR oxidation breaks these H-bonds, reorients the monomers and moves the major groove recognition α4 and α4′ helices ∼4 Å towards each other. This is the first crystal structure of a redox-sensing MarR/DUF24 family protein in bacteria that is activated by NaOCl stress. Since hypochloric acid is released by activated macrophages, related HypR-like regulators could function to protect pathogens against the host immune defense. |
format | Online Article Text |
id | pubmed-3351151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33511512012-05-14 Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR Palm, Gottfried J. Khanh Chi, Bui Waack, Paul Gronau, Katrin Becher, Dörte Albrecht, Dirk Hinrichs, Winfried Read, Randy J. Antelmann, Haike Nucleic Acids Res Structural Biology Bacillus subtilis encodes redox-sensing MarR-type regulators of the OhrR and DUF24-families that sense organic hydroperoxides, diamide, quinones or aldehydes via thiol-based redox-switches. In this article, we characterize the novel redox-sensing MarR/DUF24-family regulator HypR (YybR) that is activated by disulphide stress caused by diamide and NaOCl in B. subtilis. HypR controls positively a flavin oxidoreductase HypO that confers protection against NaOCl stress. The conserved N-terminal Cys14 residue of HypR has a lower pK(a) of 6.36 and is essential for activation of hypO transcription by disulphide stress. HypR resembles a 2-Cys-type regulator that is activated by Cys14–Cys49′ intersubunit disulphide formation. The crystal structures of reduced and oxidized HypR proteins were resolved revealing structural changes of HypR upon oxidation. In reduced HypR a hydrogen-bonding network stabilizes the reactive Cys14 thiolate that is 8–9 Å apart from Cys49′. HypR oxidation breaks these H-bonds, reorients the monomers and moves the major groove recognition α4 and α4′ helices ∼4 Å towards each other. This is the first crystal structure of a redox-sensing MarR/DUF24 family protein in bacteria that is activated by NaOCl stress. Since hypochloric acid is released by activated macrophages, related HypR-like regulators could function to protect pathogens against the host immune defense. Oxford University Press 2012-05 2012-01-11 /pmc/articles/PMC3351151/ /pubmed/22238377 http://dx.doi.org/10.1093/nar/gkr1316 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Palm, Gottfried J. Khanh Chi, Bui Waack, Paul Gronau, Katrin Becher, Dörte Albrecht, Dirk Hinrichs, Winfried Read, Randy J. Antelmann, Haike Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR |
title | Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR |
title_full | Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR |
title_fullStr | Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR |
title_full_unstemmed | Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR |
title_short | Structural insights into the redox-switch mechanism of the MarR/DUF24-type regulator HypR |
title_sort | structural insights into the redox-switch mechanism of the marr/duf24-type regulator hypr |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351151/ https://www.ncbi.nlm.nih.gov/pubmed/22238377 http://dx.doi.org/10.1093/nar/gkr1316 |
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