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Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges

Bacteria possess a large number of signal transduction systems that sense and respond to different environmental cues. Most frequently these are transcriptional regulators, two-component systems and chemosensory pathways. A major bottleneck in the field of signal transduction is the lack of informat...

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Autores principales: Martín-Mora, David, Fernández, Matilde, Velando, Félix, Ortega, Álvaro, Gavira, José A., Matilla, Miguel A., Krell, Tino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321045/
https://www.ncbi.nlm.nih.gov/pubmed/30486299
http://dx.doi.org/10.3390/ijms19123755
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author Martín-Mora, David
Fernández, Matilde
Velando, Félix
Ortega, Álvaro
Gavira, José A.
Matilla, Miguel A.
Krell, Tino
author_facet Martín-Mora, David
Fernández, Matilde
Velando, Félix
Ortega, Álvaro
Gavira, José A.
Matilla, Miguel A.
Krell, Tino
author_sort Martín-Mora, David
collection PubMed
description Bacteria possess a large number of signal transduction systems that sense and respond to different environmental cues. Most frequently these are transcriptional regulators, two-component systems and chemosensory pathways. A major bottleneck in the field of signal transduction is the lack of information on signal molecules that modulate the activity of the large majority of these systems. We review here the progress made in the functional annotation of sensor proteins using high-throughput ligand screening approaches of purified sensor proteins or individual ligand binding domains. In these assays, the alteration in protein thermal stability following ligand binding is monitored using Differential Scanning Fluorimetry. We illustrate on several examples how the identification of the sensor protein ligand has facilitated the elucidation of the molecular mechanism of the regulatory process. We will also discuss the use of virtual ligand screening approaches to identify sensor protein ligands. Both approaches have been successfully applied to functionally annotate a significant number of bacterial sensor proteins but can also be used to study proteins from other kingdoms. The major challenge consists in the study of sensor proteins that do not recognize signal molecules directly, but that are activated by signal molecule-loaded binding proteins.
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spelling pubmed-63210452019-01-07 Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges Martín-Mora, David Fernández, Matilde Velando, Félix Ortega, Álvaro Gavira, José A. Matilla, Miguel A. Krell, Tino Int J Mol Sci Review Bacteria possess a large number of signal transduction systems that sense and respond to different environmental cues. Most frequently these are transcriptional regulators, two-component systems and chemosensory pathways. A major bottleneck in the field of signal transduction is the lack of information on signal molecules that modulate the activity of the large majority of these systems. We review here the progress made in the functional annotation of sensor proteins using high-throughput ligand screening approaches of purified sensor proteins or individual ligand binding domains. In these assays, the alteration in protein thermal stability following ligand binding is monitored using Differential Scanning Fluorimetry. We illustrate on several examples how the identification of the sensor protein ligand has facilitated the elucidation of the molecular mechanism of the regulatory process. We will also discuss the use of virtual ligand screening approaches to identify sensor protein ligands. Both approaches have been successfully applied to functionally annotate a significant number of bacterial sensor proteins but can also be used to study proteins from other kingdoms. The major challenge consists in the study of sensor proteins that do not recognize signal molecules directly, but that are activated by signal molecule-loaded binding proteins. MDPI 2018-11-26 /pmc/articles/PMC6321045/ /pubmed/30486299 http://dx.doi.org/10.3390/ijms19123755 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martín-Mora, David
Fernández, Matilde
Velando, Félix
Ortega, Álvaro
Gavira, José A.
Matilla, Miguel A.
Krell, Tino
Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges
title Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges
title_full Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges
title_fullStr Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges
title_full_unstemmed Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges
title_short Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges
title_sort functional annotation of bacterial signal transduction systems: progress and challenges
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321045/
https://www.ncbi.nlm.nih.gov/pubmed/30486299
http://dx.doi.org/10.3390/ijms19123755
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