Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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HTH_LUXR helix_turn_helix, Lux Regulon

SMART accession number:	SM00421
Description:	lux regulon (activates the bioluminescence operon
Interpro abstract (IPR000792):	This domain is a DNA-binding, helix-turn-helix (HTH) domain of about 65 amino acids, present in transcription regulators of the LuxR/FixJ family of response regulators. The domain is named after Vibrio fischeri luxR, a transcriptional activator for quorum-sensing control of luminescence. LuxR-type HTH domain proteins occur in a variety of organisms. The DNA-binding HTH domain is usually located in the C-terminal region; the N-terminal region often containing an autoinducer-binding domain or a response regulatory domain. Most luxR-type regulators act as transcription activators, but some can be repressors or have a dual role for different sites. LuxR-type HTH regulators control a wide variety of activities in various biological processes. The luxR-type, DNA-binding HTH domain forms a four-helical bundle structure. The HTH motif comprises the second and third helices, known as the scaffold and recognition helix, respectively. The HTH binds DNA in the major groove, where the N-terminal part of the recognition helix makes most of the DNA contacts. The fourth helix is involved in dimerisation of gerE and traR. Signalling events by one of the four activation mechanisms described below lead to multimerisation of the regulator. The regulators bind DNA as multimers [ (PUBMED:11243786) (PUBMED:12740396) (PUBMED:12087407) ]. LuxR-type HTH proteins can be activated by one of four different mechanisms: 1) Regulators which belong to a two-component sensory transduction system where the protein is activated by its phosphorylation, generally on an aspartate residue, by a transmembrane kinase [ (PUBMED:12352954) (PUBMED:12162958) ]. Some proteins that belong to this category are: Rhizobiaceae fixJ (global regulator inducing expression of nitrogen-fixation genes in microaerobiosis) Escherichia coli and Salmonella typhimurium uhpA (activates hexose phosphate transport gene uhpT) E. coli narL and narP (activate nitrate reductase operon) Enterobacteria rcsB (regulation of exopolysaccharide biosynthesis in enteric and plant pathogenesis) Bordetella pertussis bvgA (virulence factor) Bacillus subtilis coma (involved in expression of late-expressing competence genes) 2) Regulators which are activated, or in very rare cases repressed, when bound to N-acyl homoserine lactones, which are used as quorum sensing molecules in a variety of Gram-negative bacteria [ (PUBMED:15255890) ]: V. fischeri luxR (activates bioluminescence operon) Agrobacterium tumefaciens traR (regulation of Ti plasmid transfer) Erwinia carotovora carR (control of carbapenem antibiotics biosynthesis) E. carotovora expR (virulence factor for soft rot disease; activates plant tissue macerating enzyme genes) Pseudomonas aeruginosa lasR (activates elastase gene lasB) Erwinia chrysanthemi echR and Erwinia stewartii esaR Pseudomonas chlororaphis phzR (positive regulator of phenazine antibiotic production) Pseudomonas aeruginosa rhlR (activates rhlAB operon and lasB gene) 3) Autonomous effector domain regulators, without a regulatory domain, represented by gerE [ (PUBMED:11243786) ]. 4) Multiple ligand-binding regulators, exemplified by malT [ (PUBMED:11931562) ].
GO process:	regulation of transcription, DNA-templated (GO:0006355)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 244814 HTH_LUXR domains in 244033 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing HTH_LUXR domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with HTH_LUXR domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing HTH_LUXR domain in the selected taxonomic class.

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Baikalov I, Schroder I, Kaczor-Grzeskowiak M, Grzeskowiak K, Gunsalus RP, Dickerson RE
  • Structure of the Escherichia coli response regulator NarL.
  • Biochemistry. 1996; 35: 11053-61
  • Display abstract

  • The crystal structure analysis of the NarL protein provides a first look at interactions between receiver and effector domains of a full-length bacterial response regulator. The N-terminal receiver domain, with 131 amino acids, is folded into a 5-strand beta sheet flanked by 5 alpha helices, as seen in CheY and in the N-terminal domain of NTRC. The C-terminal DNA-binding domain, with 62 amino acids, is a compact bundle of 4 alpha helices, of which the middle 2 form a helix-turn-helix motif closely related to that of Drosophila paired protein and other H-T-H DNA-binding proteins. The 2 domains are connected by an alpha helix of 10 amino acids and a 13-residue flexible tether that is not visible and presumably disordered in the X-ray structure. In this unphosphorylated form of NarL, the C-terminal domain is turned against the receiver domain in a manner that would preclude DNA binding. Activation of NarL via phosphorylation of Asp59 must involve transfer of information to the interdomain interface and either rotation or displacement of the DNA-binding C-terminal domain. Docking of a B-DNA duplex against the isolated C-terminal domain in the manner observed in paired protein and other H-T-H proteins suggests a stereochemical basis for DNA sequence preference: T-R-C-C-Y (high affinity) or T-R-C-T-N (low affinity), which is close to the experimentally observed consensus sequence: T-A-C-Y-N. The NarL structure is a model for other members of the FixJ or LuxR family of bacterial transcriptional activators, and possibly to the more distant OmpR and NtrC families as well.

  • Sitnikov DM, Schineller JB, Baldwin TO
  • Transcriptional regulation of bioluminesence genes from Vibrio fischeri.
  • Mol Microbiol. 1995; 17: 801-12
  • Display abstract

  • The phenomenon of cell-density-dependent control of gene expression, called autoinduction, has long been a subject of interest and investigation in bioluminescent marine bacteria. It is now becoming clear that many other bacteria, including animal and plant pathogens, use an autoinduction mechanism to regulate a variety of functions. Cell-density-dependent gene expression provides an excellent example of multicellular behaviour in the prokaryotic kingdom where a single cell is able to communicate and sense when a minimal population unit, a 'quorum' of bacteria, is achieved in order for certain behaviour of the population to be performed efficiently. Regulation of bacterial bioluminescence has been studied for many years and represents the best model system for understanding the mechanism of cell-density-dependent gene expression. This review will focus on transcriptional regulation of the Vibrio fischeri luminescence genes emphasizing the role of the transcriptional activator LuxR and possible autoinduction mechanisms that occur in E. coli. Alternative views and opinions regarding the molecular details of the autoinduction mechanism will be discussed.

  • Kahn D, Ditta G
  • Modular structure of FixJ: homology of the transcriptional activator domain with the -35 binding domain of sigma factors.
  • Mol Microbiol. 1991; 5: 987-97
  • Display abstract

  • The FixL/FixJ two-component system is a global regulator of nitrogen-fixation genes in Rhizobium meliloti. The transcriptional activator FixJ contains two modules: its N-terminal module is homologous with other two-component regulators; its C-terminal module shows homology with various transcriptional activators, and with the C-terminal region of sigma factors, which is involved in the discrimination of the -35 region of bacterial promoters. We show that the C-terminal module of FixJ contains the entire transcription activation function, and that the N-terminal module regulates this activity negatively. Oligonucleotide-directed mutagenesis of the transcriptional activator module demonstrated the importance of a potential helix-turn-helix structure.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 97.51 map02020 Two-component system - General 0.31 map00680 Methane metabolism 0.31 map03020 RNA polymerase 0.31 map00650 Butanoate metabolism 0.31 map00960 Alkaloid biosynthesis II 0.31 map02030 Bacterial chemotaxis - General 0.31 map00633 Trinitrotoluene degradation 0.31 map00623 2,4-Dichlorobenzoate degradation 0.31 map00630 Glyoxylate and dicarboxylate metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with HTH_LUXR domain which could be assigned to a KEGG orthologous group, and not all proteins containing HTH_LUXR domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of HTH_LUXR domains in PDB

  PDB code	Main view	Title
  1a04		THE STRUCTURE OF THE NITRATE/NITRITE RESPONSE REGULATOR PROTEIN NARL IN THE MONOCLINIC C2 CRYSTAL FORM
  1fse		CRYSTAL STRUCTURE OF THE BACILLUS SUBTILIS REGULATORY PROTEIN GERE
  1h0m		Three-dimensional structure of the quorum sensing protein TraR bound to its autoinducer and to its target DNA
  1je8		Two-Component response regulator NarL/DNA Complex: DNA Bending Found in a High Affinity Site
  1l3l		Crystal structure of a bacterial quorum-sensing transcription factor complexed with pheromone and DNA
  1p4w		Solution structure of the DNA-binding domain of the Erwinia amylovora RcsB protein
  1rnl		THE NITRATE/NITRITE RESPONSE REGULATOR PROTEIN NARL FROM NARL
  1x3u		Solution structure of the C-terminal transcriptional activator domain of FixJ from Sinorhizobium melilot
  1yio		Crystallographic structure of response regulator StyR from Pseudomonas fluorescens
  1zg1		NarL complexed to nirB promoter non-palindromic tail-to-tail DNA site
  1zg5		NarL complexed to narG-89 promoter palindromic tail-to-tail DNA site
  1zlj		Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain
  1zlk		Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain-DNA Complex
  1zn2		Low Resolution Structure of Response Regulator StyR
  2jpc		SSRB DNA Binding Protein
  2krf		NMR solution structure of the DNA binding domain of Competence protein A
  2q0o		Crystal structure of an anti-activation complex in bacterial quorum sensing
  2rnj		NMR Structure of The S. Aureus VraR DNA Binding Domain
  3c3w		Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR
  3c57		Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain Crystal Form II
  3clo		Crystal structure of putative transcriptional regulator containing a LuxR DNA binding domain (NP_811094.1) from Bacteroides thetaiotaomicron VPI-5482 at 2.04 A resolution
  3kln		Vibrio cholerae VpsT
  3klo		Vibrio cholerae VpsT bound to c-di-GMP
  3p7n		Crystal structure of light activated transcription factor El222 from Erythrobacter litoralis
  3qp5		Crystal structure of CviR bound to antagonist chlorolactone (CL)
  3qp6		Crystal structure of CviR (Chromobacterium violaceum 12472) bound to C6-HSL
  3szt		Quorum Sensing Control Repressor, QscR, Bound to N-3-oxo-dodecanoyl-L-Homoserine Lactone
  3ulq		Crystal Structure of the Anti-Activator RapF Complexed with the Response Regulator ComA DNA Binding Domain
  4gvp		Crystal Structure of the Response Regulator Protein VraR from Staphylococcus aureus
  4hye		Crystal structure of a response regulator spr1814 from Streptococcus pneumoniae reveals unique interdomain contacts among NarL family proteins
  4if4		Crystal Structure of the Magnesium and beryllofluoride-activated VraR from Staphylococcus aureus
  4ldz		4LDZ
  4lfu		Crystal structure of Escherichia coli SdiA in the space group C2
  4lgw		Crystal structure of Escherichia coli SdiA in the space group P6522
  4wsz		4WSZ
  4wt0		4WT0
  4wu4		4WU4
  4wuh		4WUH
  4wul		4WUL
  4y13		4Y13
  4y15		4Y15
  4y17		4Y17
  4yn8		4YN8
  4zmr		4ZMR
  4zms		4ZMS
  5f64		5F64
  5hev		5HEV

• Links (links to other resources describing this domain)

• INTERPRO	IPR000792
  PFAM	GerE
  PROSITE	HTH_LUXR_FAMILY

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