Fig 1.
Canonical LuxIR-type quorum sensing (QS) system in Gram-negative bacteria.
At low cell density (LCD; left panel), LuxR, a LuxR-type transcription factor (light-green ovals), remains inactive due to the absence of its cognate autoinducer, an acyl-homoserine lactone (AHL) signal (light-green pentagons). LuxI, the autoinducer synthase (light-green squares), constitutively produces AHLs at basal levels that accumulate in the extracellular environment. At LCD, AHL concentration is insufficient to activate LuxR or trigger a population-level response. At high cell density (HCD; right panel), AHL levels are elevated and diffuse back into cells, enabling binding to LuxR, which promotes receptor folding and dimerization, DNA binding, and activation of LuxR-dependent genes, including those involved in virulence. Activated LuxR promotes transcription of its own gene and luxI, establishing a positive feedback loop that amplifies QS. For simplicity, LuxR is depicted as a monomer, though it functions as a dimer when bound to AHL. The red “X” in the LCD panel indicates that LuxR is inactive and unable to bind DNA or activate transcription in the absence of sufficient AHL. The chemical structure of a basic AHL is shown in black. All AHLs contain a homoserine lactone ring and an acyl side chain that varies in length (n), oxidation state, and the presence of substituents (X). Created in BioRender. Paczkowski, J. (2026) https://BioRender.com/bzj00cg.
Fig 2.
Conserved structural and sequence features of LuxR-type quorum sensing receptors.
(A) Structural model of P. aeruginosa RhlR, highlighting the modular architecture that defines LuxR-type receptors: an N-terminal acyl-homoserine lactone (AHL) ligand-binding domain (LBD; turquoise) and a C-terminal helix-turn-helix (HTH) DNA-binding domain (DBD; yellow). The solvent-accessible volume of the LBD ligand-binding pocket is shown in light pink to provide structural context. Structures are derived from PDB IDs 8DQ0 and 8DQ1 [82], and all structure images were generated using ChimeraX. (B) Panel of AHL signal molecules recognized by the cognate receptors as in panel C. C4-HSL; P. aeruginosa; RhlR, C6-HSL; C. subtsugae; CviR, 3OC8-HSL; A. tumefaciens; TraR, 3OC12-HSL; LasR; 3OHC12-HSL; A. baumannii; AbaR. (C) Multiple sequence alignment (MSA) of LuxR-type receptors discussed in this review, spanning residues 44–72, which correspond to a conserved portion of the LBD. Amino acids are colored by physicochemical properties (positive, negative, polar, and non-polar, as indicated). A maximum-likelihood phylogenetic tree based on full-length sequences is shown to the left of the alignment. (D) Sequence alignment of the HTH DNA binding domains (residues 198–217) from the same set of receptors shown in panel B. The phylogenetic tree is omitted for clarity. Conserved residues within the HTH motif are denoted with an asterisk.
Fig 3.
LuxR-type receptors are subject to diverse regulatory protein-protein interaction mechanisms that influence their activity as transcriptional regulators.
LuxR-type QS receptors (light-green ovals) are subject to regulation by a range of protein interaction partners (purple ovals), which modulate receptor function through distinct mechanisms. Negative regulators inhibit LuxR-type receptor function by disrupting dimerization, decreasing receptor stability, and inhibiting DNA binding. Representative examples include TraM-TraR (A. tumefaciens), QscR-LasR/RhlR QteE-LasR/RhlR, Aqs1-LasR (all P.s aeruginosa), and VioS-CviR (C. subtsugae). Dual or context-dependent regulators modify LuxR-type receptor activity in a promoter-, ligand-, or environmental-dependent manner. Examples include PqsE-RhlR (P. aeruginosa) and BlsA-AbaR (A. baumannii), which increase DNA binding affinity and/or transcriptional output under specific conditions. Global regulators modulate LuxR-type receptor function through transcriptional engagement or post-translational control, including RNA polymerase-mediated activation and protease-dependent receptor degradation. Created in BioRender. Paczkowski, J. (2026) https://BioRender.com/akj8r1w.
Fig 4.
Structural basis of anti-activation in LuxR-type quorum sensing receptors.
(A) Structure of TraM-TraR complex from homologous Rhizobium sp. strain NGR234 proteins (PDB ID: 2Q0O [49]). Shown sequentially are: TraR homodimer alone (red), TraR homodimer (blue), and the full 2:2 TraM-TraR complex. TraM functions as an anti-activator by binding to TraR, inducing an allosteric conformational change in the protein and preventing DNA binding. (B) Structure of the QslA-LasR ligand-binding domain (LBD) complex from Pseudomonas aeruginosa (PDB ID: 4NG2 [61]). The complex consists of 2:1 stoichiometry, with a QslA homodimer (blue and gray) interacting with a single monomer of the LasR LBD (cyan), obstructing dimer formation and preventing LasR activation. (C) Structure of Aqs1-LasR complex from P. aeruginosa (PDB ID: 6V7W [30]). The complex consists of an Aqs1 dimer which binds to the DNA-binding domain of a LasR monomer preventing DNA binding. These co-crystal structures illustrate distinct anti-activation mechanisms: disruption of DNA binding (TraM-TraR and Aqs1-LasR), and disruption of receptor dimerization (QslA-LasR). All structure images were generated using ChimeraX.
Fig 5.
Structural comparison of LuxR-type context-dependent regulators.
(A) Cartoon representation of a PqsE monomer (purple; PDB ID: 7KGW [28]) rotated 90° on its axis and colored by rainbow from the N-terminus to the C-terminus. Highlighted are conserved C-terminal alpha helices, α5–α9, that are unique among this class of enzymes. (B) Cartoon representation of BlsA (blue; PDB ID: 6W6Z [105]) in the ground state, rotated by 90° on its axis and colored by rainbow from the N-terminus to the C-terminus. Highlighted is the secondary structure of BlsA, which is notably different compared to PqsE. All structure images were generated using ChimeraX.
Fig 6.
Canonical and accessory protein dependent models of LuxR-RNAP recruitment.
Canonical LuxR proteins recruit RNAP directly when bound to promoter-proximal lux boxes, typically upstream of the -35 element (left), as established in Vibrio species. In contrast, some LuxR-type receptors may require accessory proteins to enable transcription potentially through RNAP recruitment, modulation of DNA binding, or promoter specificity (right). This accessory-mediated mechanism remains hypothetical and likely reflects a layer of context-dependent regulation. Created in BioRender. Paczkowski, J. (2026) https://BioRender.com/kv3bnqa.