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The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket
The BarA/UvrY two-component signal transduction system is widely conserved in γ-proteobacteria and provides a link between the metabolic state of the cells and the Csr posttranscriptional regulatory system. In Escherichia coli, the BarA/UvrY system responds to the presence of acetate and other short...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639471/ https://www.ncbi.nlm.nih.gov/pubmed/34743001 http://dx.doi.org/10.1016/j.jbc.2021.101383 |
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author | Alvarez, Adrián F. Rodríguez, Claudia González-Chávez, Ricardo Georgellis, Dimitris |
author_facet | Alvarez, Adrián F. Rodríguez, Claudia González-Chávez, Ricardo Georgellis, Dimitris |
author_sort | Alvarez, Adrián F. |
collection | PubMed |
description | The BarA/UvrY two-component signal transduction system is widely conserved in γ-proteobacteria and provides a link between the metabolic state of the cells and the Csr posttranscriptional regulatory system. In Escherichia coli, the BarA/UvrY system responds to the presence of acetate and other short-chain carboxylic acids by activating transcription of the noncoding RNAs, CsrB and CsrC, which sequester the RNA-binding protein CsrA, a global regulator of gene expression. However, the state of the carboxyl group in the acetate molecule, which serves as the BarA stimulus, and the signal reception site of BarA remain unknown. In this study, we show that the deletion or replacement of the periplasmic domain of BarA and also the substitution of certain hydroxylated and hydrophobic amino acid residues in this region, result in a sensor kinase that remains unresponsive to its physiological stimulus, demonstrating that the periplasmic region of BarA constitutes a functional detector domain. Moreover, we provide evidence that the protonated state of acetate or formate serves as the physiological stimulus of BarA. In addition, modeling of the BarA sensor domain and prediction of the signal-binding site, by blind molecular docking, revealed a calcium channels and chemotaxis receptors domain with a conserved binding pocket, which comprised uncharged polar and hydrophobic amino acid residues. Based on the comparative sequence and phylogenetic analyses, we propose that, at least, two types of BarA orthologues diverged and evolved separately to acquire distinct signal-binding properties, illustrating the wide adaptability of the bacterial sensor kinase proteins. |
format | Online Article Text |
id | pubmed-8639471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-86394712021-12-09 The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket Alvarez, Adrián F. Rodríguez, Claudia González-Chávez, Ricardo Georgellis, Dimitris J Biol Chem Research Article The BarA/UvrY two-component signal transduction system is widely conserved in γ-proteobacteria and provides a link between the metabolic state of the cells and the Csr posttranscriptional regulatory system. In Escherichia coli, the BarA/UvrY system responds to the presence of acetate and other short-chain carboxylic acids by activating transcription of the noncoding RNAs, CsrB and CsrC, which sequester the RNA-binding protein CsrA, a global regulator of gene expression. However, the state of the carboxyl group in the acetate molecule, which serves as the BarA stimulus, and the signal reception site of BarA remain unknown. In this study, we show that the deletion or replacement of the periplasmic domain of BarA and also the substitution of certain hydroxylated and hydrophobic amino acid residues in this region, result in a sensor kinase that remains unresponsive to its physiological stimulus, demonstrating that the periplasmic region of BarA constitutes a functional detector domain. Moreover, we provide evidence that the protonated state of acetate or formate serves as the physiological stimulus of BarA. In addition, modeling of the BarA sensor domain and prediction of the signal-binding site, by blind molecular docking, revealed a calcium channels and chemotaxis receptors domain with a conserved binding pocket, which comprised uncharged polar and hydrophobic amino acid residues. Based on the comparative sequence and phylogenetic analyses, we propose that, at least, two types of BarA orthologues diverged and evolved separately to acquire distinct signal-binding properties, illustrating the wide adaptability of the bacterial sensor kinase proteins. American Society for Biochemistry and Molecular Biology 2021-11-04 /pmc/articles/PMC8639471/ /pubmed/34743001 http://dx.doi.org/10.1016/j.jbc.2021.101383 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Alvarez, Adrián F. Rodríguez, Claudia González-Chávez, Ricardo Georgellis, Dimitris The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket |
title | The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket |
title_full | The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket |
title_fullStr | The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket |
title_full_unstemmed | The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket |
title_short | The Escherichia coli two-component signal sensor BarA binds protonated acetate via a conserved hydrophobic-binding pocket |
title_sort | escherichia coli two-component signal sensor bara binds protonated acetate via a conserved hydrophobic-binding pocket |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639471/ https://www.ncbi.nlm.nih.gov/pubmed/34743001 http://dx.doi.org/10.1016/j.jbc.2021.101383 |
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