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Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain

Bacteria possess transcription regulators (of the TetR family) specifically dedicated to repressing genes for cytochrome P450, involved in oxidation of polyunsaturated fatty acids. Interaction of these repressors with operator sequences is disrupted in the presence of fatty acids, and they are there...

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Autores principales: Derouiche, Abderahmane, Bidnenko, Vladimir, Grenha, Rosa, Pigonneau, Nathalie, Ventroux, Magali, Franz-Wachtel, Mirita, Nessler, Sylvie, Noirot-Gros, Marie-Françoise, Mijakovic, Ivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814354/
https://www.ncbi.nlm.nih.gov/pubmed/23939619
http://dx.doi.org/10.1093/nar/gkt709
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author Derouiche, Abderahmane
Bidnenko, Vladimir
Grenha, Rosa
Pigonneau, Nathalie
Ventroux, Magali
Franz-Wachtel, Mirita
Nessler, Sylvie
Noirot-Gros, Marie-Françoise
Mijakovic, Ivan
author_facet Derouiche, Abderahmane
Bidnenko, Vladimir
Grenha, Rosa
Pigonneau, Nathalie
Ventroux, Magali
Franz-Wachtel, Mirita
Nessler, Sylvie
Noirot-Gros, Marie-Françoise
Mijakovic, Ivan
author_sort Derouiche, Abderahmane
collection PubMed
description Bacteria possess transcription regulators (of the TetR family) specifically dedicated to repressing genes for cytochrome P450, involved in oxidation of polyunsaturated fatty acids. Interaction of these repressors with operator sequences is disrupted in the presence of fatty acids, and they are therefore known as fatty-acid-displaced regulators. Here, we describe a novel mechanism of inactivating the interaction of these proteins with DNA, illustrated by the example of Bacillus subtilis regulator FatR. FatR was found to interact in a two-hybrid assay with TkmA, an activator of the protein-tyrosine kinase PtkA. We show that FatR is phosphorylated specifically at the residue tyrosine 45 in its helix-turn-helix domain by the kinase PtkA. Structural modelling reveals that the hydroxyl group of tyrosine 45 interacts with DNA, and we show that this phosphorylation reduces FatR DNA binding capacity. Point mutants mimicking phosphorylation of FatR in vivo lead to a strong derepression of the fatR operon, indicating that this regulatory mechanism works independently of derepression by polyunsaturated fatty acids. Tyrosine 45 is a highly conserved residue, and PtkA from B. subtilis can phosphorylate FatR homologues from other bacteria. This indicates that phosphorylation of tyrosine 45 may be a general mechanism of switching off bacterial fatty-acid-displaced regulators.
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spelling pubmed-38143542013-11-04 Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain Derouiche, Abderahmane Bidnenko, Vladimir Grenha, Rosa Pigonneau, Nathalie Ventroux, Magali Franz-Wachtel, Mirita Nessler, Sylvie Noirot-Gros, Marie-Françoise Mijakovic, Ivan Nucleic Acids Res Molecular Biology Bacteria possess transcription regulators (of the TetR family) specifically dedicated to repressing genes for cytochrome P450, involved in oxidation of polyunsaturated fatty acids. Interaction of these repressors with operator sequences is disrupted in the presence of fatty acids, and they are therefore known as fatty-acid-displaced regulators. Here, we describe a novel mechanism of inactivating the interaction of these proteins with DNA, illustrated by the example of Bacillus subtilis regulator FatR. FatR was found to interact in a two-hybrid assay with TkmA, an activator of the protein-tyrosine kinase PtkA. We show that FatR is phosphorylated specifically at the residue tyrosine 45 in its helix-turn-helix domain by the kinase PtkA. Structural modelling reveals that the hydroxyl group of tyrosine 45 interacts with DNA, and we show that this phosphorylation reduces FatR DNA binding capacity. Point mutants mimicking phosphorylation of FatR in vivo lead to a strong derepression of the fatR operon, indicating that this regulatory mechanism works independently of derepression by polyunsaturated fatty acids. Tyrosine 45 is a highly conserved residue, and PtkA from B. subtilis can phosphorylate FatR homologues from other bacteria. This indicates that phosphorylation of tyrosine 45 may be a general mechanism of switching off bacterial fatty-acid-displaced regulators. Oxford University Press 2013-11 2013-08-10 /pmc/articles/PMC3814354/ /pubmed/23939619 http://dx.doi.org/10.1093/nar/gkt709 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular Biology
Derouiche, Abderahmane
Bidnenko, Vladimir
Grenha, Rosa
Pigonneau, Nathalie
Ventroux, Magali
Franz-Wachtel, Mirita
Nessler, Sylvie
Noirot-Gros, Marie-Françoise
Mijakovic, Ivan
Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
title Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
title_full Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
title_fullStr Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
title_full_unstemmed Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
title_short Interaction of bacterial fatty-acid-displaced regulators with DNA is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
title_sort interaction of bacterial fatty-acid-displaced regulators with dna is interrupted by tyrosine phosphorylation in the helix-turn-helix domain
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814354/
https://www.ncbi.nlm.nih.gov/pubmed/23939619
http://dx.doi.org/10.1093/nar/gkt709
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