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LsrR DNA-binding transcriptional repressor

Synonyms: LsrR-(4S)-4-hydroxy-5-phosphooxypentane-2,3-dione, LsrR-autoinducer 2, LsrR, LsrR-(2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran
Summary:
Using particular analysis and high-throughput analysis (microarrays), it was established that LsrR regulates expression of many genes involved in several processes, such as autoinducer 2 uptake and processing [1, 2], biofilm architecture [1, 6], host invasion, stress responses, and foreign DNA, among others [1]. It also regulates the expression of small riboregulators [1]. LrsR pertains to the quorum-sensing system, which involves autoinducer-based bacterial cell-to-cell communication [7]. It was demonstrated in Salmonella enterica serovar Typhimurium that LsrR directly senses and binds the molecule 4,5-dihydroxy-2,3-pentanedione (DPD), phosphorylated [8] and dephosphorylated [1].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
LsrR Functional   Apo [APPH], [IEP], [IMP], [IPI] [1], [2], [3], [4]
LsrR-(2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran Non-Functional   Holo [IPI] [3]
LsrR-(4S)-4-hydroxy-5-phosphooxypentane-2,3-dione Non-Functional Allosteric Holo nd nd
LsrR-autoinducer 2 Non-Functional Allosteric Holo [IEP], [IMP] [1]
Evolutionary Family: Sugar_binding domain
Connectivity class: Local Regulator
Gene name: lsrR
  Genome position: 1600288-1601241
  Length: 954 bp / 317 aa
Operon name: lsrRK
TU(s) encoding the TF:
Transcription unit        Promoter
lsrRK
lsrRp


Regulon       
Regulated gene(s) lsrA, lsrB, lsrC, lsrD, lsrF, lsrG, lsrK, lsrR, tam
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
ABC superfamily, membrane component (2)
membrane (2)
ABC superfamily ATP binding cytoplasmic component (1)
ABC superfamily, periplasmic binding component (1)
regulation (1)
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Regulated operon(s) lsrACDBFG-tam, lsrRK
First gene in the operon(s) lsrA, lsrR
Simple and complex regulons CRP,LsrR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[LsrR,-](2)


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 (Confirmed, Strong, Weak) References
  LsrR repressor lsrAp Sigma38 11.5 -19.5 lsrA, lsrC, lsrD, lsrB, lsrF, lsrG, tam
atacatttgtTCAAAACTCACCTGCAAAACTGAACGGGGGaaatatgcaa
1601456 1601485 [BPP], [GEA], [SM] [2], [4]
  LsrR repressor lsrRp Sigma70 -18.5 -34.5 lsrR, lsrK
gagcaagaacTGAACAATTGCATTAAAGATTTAAATATGTtcaaagtgaa
1601261 1601290 [BPP], [GEA], [SM] [3], [4], [5]


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


Evidence    

 [APPH] Assay of protein purified to homogeneity

 [IEP] Inferred from expression pattern

 [IMP] Inferred from mutant phenotype

 [IPI] Inferred from physical interaction

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [SM] Site mutation



Reference(s)    

 [1] Li J, Attila C, Wang L, Wood TK, Valdes JJ, Bentley WE, 2007, Quorum sensing in Escherichia coli is signaled by AI-2/LsrR: effects on small RNA and biofilm architecture., J Bacteriol, 2007 Aug

 [2] Wang L., Hashimoto Y., Tsao CY., Valdes JJ., Bentley WE., 2005, Cyclic AMP (cAMP) and cAMP receptor protein influence both synthesis and uptake of extracellular autoinducer 2 in Escherichia coli., J Bacteriol 187(6):2066-76

 [3] Wu M., Tao Y., Liu X., Zang J., 2013, Structural basis for phosphorylated autoinducer-2 modulation of the oligomerization state of the global transcription regulator LsrR from Escherichia coli., J Biol Chem 288(22):15878-87

 [4] Xue T., Zhao L., Sun H., Zhou X., Sun B., 2009, LsrR-binding site recognition and regulatory characteristics in Escherichia coli AI-2 quorum sensing., Cell Res 19(11):1258-68

 [5] Wang L., Li J., March JC., Valdes JJ., Bentley WE., 2005, luxS-dependent gene regulation in Escherichia coli K-12 revealed by genomic expression profiling., J Bacteriol 187(24):8350-60

 [6] Zhang XS., Garcia-Contreras R., Wood TK., 2008, Escherichia coli transcription factor YncC (McbR) regulates colanic acid and biofilm formation by repressing expression of periplasmic protein YbiM (McbA)., ISME J 2(6):615-31

 [7] Fuqua WC, Winans SC, Greenberg EP, 1994, Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators., J Bacteriol, 1994 Jan

 [8] Xavier KB, Miller ST, Lu W, Kim JH, Rabinowitz J, Pelczer I, Semmelhack MF, Bassler BL, 2007, Phosphorylation and processing of the quorum-sensing molecule autoinducer-2 in enteric bacteria., ACS Chem Biol, 2007 Feb 20

 [9] Xavier KB., Bassler BL., 2005, Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli., J Bacteriol 187(1):238-48

 [10] Ha JH, Eo Y, Grishaev A, Guo M, Smith JA, Sintim HO, Kim EH, Cheong HK, Bentley WE, Ryu KS, 2013, Crystal structures of the LsrR proteins complexed with phospho-AI-2 and two signal-interrupting analogues reveal distinct mechanisms for ligand recognition., J Am Chem Soc, 2013 Oct 16

 [11] Taga ME, Miller ST, Bassler BL, 2003, Lsr-mediated transport and processing of AI-2 in Salmonella typhimurium., Mol Microbiol, 2003 Nov

 [12] Mitra A., Herren CD., Patel IR., Coleman A., Mukhopadhyay S., 2016, Integration of AI-2 Based Cell-Cell Signaling with Metabolic Cues in Escherichia coli., PLoS One 11(6):e0157532

 [13] Krisko A, Copic T, Gabaldón T, Lehner B, Supek F, 2014, Inferring gene function from evolutionary change in signatures of translation efficiency., Genome Biol, 2014 Mar 3



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