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A covariation analysis reveals elements of selectivity in quorum sensing systems
Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328516/ https://www.ncbi.nlm.nih.gov/pubmed/34180398 http://dx.doi.org/10.7554/eLife.69169 |
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author | Wellington Miranda, Samantha Cong, Qian Schaefer, Amy L MacLeod, Emily Kenna Zimenko, Angelina Baker, David Greenberg, E Peter |
author_facet | Wellington Miranda, Samantha Cong, Qian Schaefer, Amy L MacLeod, Emily Kenna Zimenko, Angelina Baker, David Greenberg, E Peter |
author_sort | Wellington Miranda, Samantha |
collection | PubMed |
description | Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system from Pseudomonas aeruginosa PAO1. The covarying residues in both proteins cluster around the ligand-binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated that covariation methods provide a powerful approach for investigating selectivity in protein-small molecule interactions and have deepened our understanding of how communication systems evolve and diversify. |
format | Online Article Text |
id | pubmed-8328516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-83285162021-08-04 A covariation analysis reveals elements of selectivity in quorum sensing systems Wellington Miranda, Samantha Cong, Qian Schaefer, Amy L MacLeod, Emily Kenna Zimenko, Angelina Baker, David Greenberg, E Peter eLife Computational and Systems Biology Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system from Pseudomonas aeruginosa PAO1. The covarying residues in both proteins cluster around the ligand-binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated that covariation methods provide a powerful approach for investigating selectivity in protein-small molecule interactions and have deepened our understanding of how communication systems evolve and diversify. eLife Sciences Publications, Ltd 2021-06-28 /pmc/articles/PMC8328516/ /pubmed/34180398 http://dx.doi.org/10.7554/eLife.69169 Text en © 2021, Wellington Miranda et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Wellington Miranda, Samantha Cong, Qian Schaefer, Amy L MacLeod, Emily Kenna Zimenko, Angelina Baker, David Greenberg, E Peter A covariation analysis reveals elements of selectivity in quorum sensing systems |
title | A covariation analysis reveals elements of selectivity in quorum sensing systems |
title_full | A covariation analysis reveals elements of selectivity in quorum sensing systems |
title_fullStr | A covariation analysis reveals elements of selectivity in quorum sensing systems |
title_full_unstemmed | A covariation analysis reveals elements of selectivity in quorum sensing systems |
title_short | A covariation analysis reveals elements of selectivity in quorum sensing systems |
title_sort | covariation analysis reveals elements of selectivity in quorum sensing systems |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328516/ https://www.ncbi.nlm.nih.gov/pubmed/34180398 http://dx.doi.org/10.7554/eLife.69169 |
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