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LldR DNA-binding transcriptional dual regulator

Synonyms: LldR, LldR-(S)-lactate
Summary:
LldR, formerly named "lactate regulator", is a transcription factor that controls expression of genes involved in transport and catabolism of L-lactate [1, 4]. This regulator has a dual function and is positively and negatively autoregulated. In the absence of L-lactate and under anaerobic conditions, this regulator repressed the transcription of the lldPRD operon [1]. In this repression system, LldR binds to two operators and probably leads to repressor DNA looping [1]. Expression of this regulator is also stimulated in presence of L-lactate, and this inductor promotes a conformational change that probably destabilizes the DNA loop, promoting the transcription open complex [1]. On the another hand, the transcription of lldR is also induced upon biofilm formation compared to planktonic growth in both exponential and stationary phases. An lctR mutant is impaired in biofilm formation [5].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
LldR Functional   Apo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP-SITE-MUTATION], [EXP-IPI] S [1]
LldR-(S)-lactate Functional Allosteric Holo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP-SITE-MUTATION], [EXP-IPI] S [1]
Evolutionary Family: GntR
TFBs length: 23
TFBs symmetry: inverted-repeat
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: lldR
  Genome position: 3779054-3779830
  Length: 777 bp / 258 aa
Operon name: lldPRD
TU(s) encoding the TF:
Transcription unit        Promoter
lldPRD
lldPp


Regulon       
Regulated gene(s) lldD, lldP, lldR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
aerobic respiration (2)
anaerobic respiration (1)
electron donors (1)
carbon compounds (1)
Porters (Uni-, Sym- and Antiporters) (1)
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Regulated operon(s) lldPRD
First gene in the operon(s) lldP
Simple and complex regulons ArcA,LldR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[LldR,+](1)
[LldR,-](1)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  LldR repressor lldPp Sigma70 -97.0 -207.0 lldP, lldR, lldD
ctccccccacAAGAATTGGCCCTACCAATTCTTcgcttatctg
 3777181 3777203 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2]
  LldR-(S)-lactate activator lldPp Sigma70 -97.0 -207.0 lldP, lldR, lldD
ctccccccacAAGAATTGGCCCTACCAATTCTTcgcttatctg
 3777181 3777203 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [2]
  LldR repressor lldPp Sigma70 30.0 -81.0 lldP, lldR, lldD
ccctacacaaCACAATTGGCAGTGCCACTTTTAcacaacgtgt
 3777307 3777329 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [1], [1], [3], [3]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation


Evidence    

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-IMP-SITE-MUTATION] Site mutation

 [EXP-IPI] Inferred from physical interaction

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.


Reference(s)    

 [1] Aguilera L., Campos E., Gimenez R., Badia J., Aguilar J., Baldoma L., 2008, Dual role of LldR in regulation of the lldPRD operon, involved in L-lactate metabolism in Escherichia coli., J Bacteriol 190(8):2997-3005

 [2] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [3] Lynch AS., Lin EC., 1996, Transcriptional control mediated by the ArcA two-component response regulator protein of Escherichia coli: characterization of DNA binding at target promoters., J Bacteriol 178(21):6238-49

 [4] Dong JM., Taylor JS., Latour DJ., Iuchi S., Lin EC., 1993, Three overlapping lct genes involved in L-lactate utilization by Escherichia coli., J Bacteriol 175(20):6671-8

 [5] Beloin C., Valle J., Latour-Lambert P., Faure P., Kzreminski M., Balestrino D., Haagensen JA., Molin S., Prensier G., Arbeille B., Ghigo JM., 2004, Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression., Mol Microbiol 51(3):659-74


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