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Crystal structure of QscR, a Pseudomonas aeruginosa quorum sensing signal receptor.

ABSTRACT: Acyl-homoserine lactone (AHL) quorum sensing controls gene expression in hundreds of Proteobacteria including a number of plant and animal pathogens. Generally, the AHL receptors are members of a family of related transcription factors, and although they have been targets for development of antivirulence therapeutics there is very little structural information about this class of bacterial receptors. We have determined the structure of the transcription factor, QscR, bound to N-3-oxo-dodecanoyl-homoserine lactone from the opportunistic human pathogen Pseudomonas aeruginosa at a resolution of 2.55 ?. The ligand-bound QscR is a dimer with a unique symmetric "cross-subunit" arrangement containing multiple dimerization interfaces involving both domains of each subunit. The QscR dimer appears poised to bind DNA. Predictions about signal binding and dimerization contacts were supported by studies of mutant QscR proteins in vivo. The acyl chain of the AHL is in close proximity to the dimerization interfaces. Our data are consistent with an allosteric mechanism of signal transmission in the regulation of DNA binding and thus virulence gene expression.

SUBMITTER: Lintz MJ

PROVIDER: S-EPMC3179110 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Crystal structure of QscR, a Pseudomonas aeruginosa quorum sensing signal receptor.

Lintz Mario J MJ Oinuma Ken-ichi K Wysoczynski Christina L CL Greenberg Everett Peter EP Churchill Mair E A ME

Proceedings of the National Academy of Sciences of the United States of America 20110912 38

Acyl-homoserine lactone (AHL) quorum sensing controls gene expression in hundreds of Proteobacteria including a number of plant and animal pathogens. Generally, the AHL receptors are members of a family of related transcription factors, and although they have been targets for development of antivirulence therapeutics there is very little structural information about this class of bacterial receptors. We have determined the structure of the transcription factor, QscR, bound to N-3-oxo-dodecanoyl- ...[more]

PMID: 21911405

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Project description:Pseudomonas aeruginosa uses two acyl-homoserine lactone signals and two quorum sensing (QS) transcription factors, LasR and RhlR, to activate dozens of genes. LasR responds to N-3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and RhlR to N-butanoyl-homoserine lactone (C4-HSL). There is a third P. aeruginosa acyl-homoserine-lactone-responsive transcription factor, QscR, which acts to dampen or delay activation of genes by LasR and RhlR by an unknown mechanism. To better understand the role of QscR in P. aeruginosa QS, we performed a chromatin immunoprecipitation analysis, which showed this transcription factor bound the promoter of only a single operon of three genes linked to qscR, PA1895 to PA1897. Other genes that appear to be regulated by QscR in transcriptome studies were not direct targets of QscR. Deletion of PA1897 recapitulates the early QS activation phenotype of a QscR-null mutant, and the phenotype of a QscR-null mutant was complemented by PA1895-1897 but not by PA1897 alone. We conclude that QscR acts to modulate quorum sensing through regulation of a single operon, apparently raising the QS threshold of the population and providing a "brake" on QS autoinduction.IMPORTANCE Quorum sensing, a cell-cell communication system, is broadly distributed among bacteria and is commonly used to regulate the production of shared products. An important consequence of quorum sensing is a delay in production of certain products until the population density is high. The bacterium Pseudomonas aeruginosa has a particularly complicated quorum sensing system involving multiple signals and receptors. One of these receptors, QscR, downregulates gene expression, unlike the other receptors in P. aeruginosa QscR does so by inducing the expression of a single operon whose function provides an element of resistance to a population reaching a quorum. This finding has importance for design of quorum sensing inhibitory strategies and can also inform design of synthetic biological circuits that use quorum sensing receptors to regulate gene expression.

Project description:Many Proteobacteria govern responses to changes in cell density by using acyl-homoserine lactone (AHL) quorum-sensing (QS) signaling. Similar to the LuxI-LuxR system described in Vibrio fischeri, a minimal AHL QS circuit comprises a pair of genes, a luxI-type synthase gene encoding an enzyme that synthesizes an AHL and a luxR-type AHL-responsive transcription regulator gene. In most bacteria that utilize AHL QS, cognate luxI and luxR homologs are found in proximity to each other on the chromosome. However, a number of recent reports have identified luxR homologs that are not linked to luxI homologs; in some cases luxR homologs have been identified in bacteria that have no luxI homologs. A luxR homolog without a linked luxI homologs is termed an orphan or solo. One of the first reports of an orphan was on QscR in Pseudomonas aeruginosa. The qscR gene was revealed by whole genome sequencing and has been studied in some detail. P. aeruginosa encodes two AHL synthases and three AHL responsive receptors, LasI-LasR form a cognate synthase-receptor pair as do RhlI-RhlR. QscR lacks a linked synthase and responds to the LasI-generated AHL. QS regulation of gene expression in P. aeruginosa employs multiple signals and occurs in the context of other interconnected regulatory circuits that control diverse physiological functions. QscR affects virulence of P. aeruginosa, and although it shows sensitivity to the LasI-generated AHL, 3-oxo-dodecanoylhomoserine lactone, it's specificity is relaxed compared to LasR and can respond equally well to several AHLs. QscR controls a set of genes that overlaps the set regulated by LasR. QscR is comparatively easy to purify and study in vitro, and has become a model for understanding the biochemistry of LuxR homologs. In fact there is a crystal structure of QscR bound to the LasI-generated AHL. Here, we review the current state of research concerning QscR and highlight recent advances in our understanding of its structure and biochemistry.

Dataset Information

Crystal structure of QscR, a Pseudomonas aeruginosa quorum sensing signal receptor.

Publications

Crystal structure of QscR, a Pseudomonas aeruginosa quorum sensing signal receptor.

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