title: Reversible signal binding by the Pseudomonas aeruginosa quorum-sensing signal receptor LasR.
abstract: Many members of the LuxR family of acyl-homoserine lactone (acyl-HSL)-dependent quorum-sensing transcriptional activators are thought to have the unusual characteristics of requiring the signal ligand during polypeptide synthesis to fold into an active conformation and of binding signal extraordinarily tightly. This is the case for the N-3-oxo-dodecanoyl-HSL-dependent Pseudomonas aeruginosa virulence regulator LasR. We present evidence that LasR can fold into an active conformation in vivo in the absence of the acyl-HSL ligand. We also present evidence indicating that in the cellular environment, LasR and N-3-oxo-dodecanoyl-HSL readily dissociate. After dissociation, LasR can remain in a properly folded conformation capable of reassociating with signal. We present a new model for the folding and signal binding of LasR and other members of the family of transcription factors to which LasR belongs. Our findings have important implications concerning the cellular responses to decreased environmental concentrations of signals and have implications about potential quorum-sensing inhibition strategies.
authors.affiliation: Department of Microbiology, University of Washington, School of Medicine, Seattle, Washington, USA.
authors.forename: Kaia J
authors.initials: KJ
authors.lastname: Sappington
authors.forename: Ajai A
authors.initials: AA
authors.lastname: Dandekar
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Oinuma
authors.forename: E Peter
authors.initials: EP
authors.lastname: Greenberg
mesh_terms: D054742:Acyl-Butyrolactones / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D011485:Protein Binding; D017510:Protein Folding; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053038:Quorum Sensing; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators