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LacI DNA-binding transcriptional repressor

Synonyms: LacI, LacI-allolactose
Summary:
The Lactose inhibitor, LacI, is a DNA-binding transcription factor that represses transcription of the operon involved in transport and catabolism of lactose [6, 8, 9]. In the absence of allolactose, LacI represses the lac operon by preventing open promoter complex formation for transcription [8, 10]. In this repression system, LacI binds to two operators, and formation of the repressor loop is critical [8, 11, 12, 13]. This repressor binds in tandem to inverted repeat sequences that are 21 nucleotides long and possess conserved motifs [8, 11, 12]. LacI is negatively autoregulated when it binds to two DNA-binding sites, one located downstream of the lacI gene and the other one located in the coding sequence for the C terminus of LacI. The protein when bound to these sites forms a loop that inhibits the transcription elongation, thus producing truncated proteins that are tagged for degradation by the small peptide SsrA [14, 15] .
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
LacI Functional   Apo [IPI] [1]
LacI-allolactose Non-Functional Allosteric Holo [IPI] [1]
Evolutionary Family: GalR/LacI
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: lacI
  Genome position: 366428-367510
  Length: 1083 bp / 360 aa
Operon name: mhpR-lacI
TU(s) encoding the TF:
Transcription unit        Promoter
lacI
lacIp
mhpR-lacI
mhpRp
mhpR-lacI
mhpRp1


Regulon       
Regulated gene(s) lacA, lacY, lacZ
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (3)
Porters (Uni-, Sym- and Antiporters) (1)
membrane (1)
Regulated operon(s) lacZYA
First gene in the operon(s) lacZ
Simple and complex regulons CRP,H-NS,LacI
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[LacI,-](1)


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
  LacI repressor lacZp1 Sigma70 -82.0 -120.0 lacZ, lacY, lacA
ctggaaagcgGGCAGTGAGCGCAACGCAATTaatgtgagtt
366415 366435 [HIBSCS], [SM] [2], [3], [4]
  LacI repressor lacZp1 Sigma70 11.0 -28.0 lacZ, lacY, lacA
tgttgtgtggAATTGTGAGCGGATAACAATTtcacacagga
366323 366343 [HIBSCS], [SM] [2], [4], [5], [6], [7]
  LacI repressor lacZp1 Sigma70 412.0 373.0 lacZ, lacY, lacA
gaatccgacgGGTTGTTACTCGCTCACATTTaatgttgatg
365922 365942 [HIBSCS], [SM] [2], [4], [6]


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


Evidence    

 [IPI] Inferred from physical interaction

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation



Reference(s)    

 [1] Daber R., Stayrook S., Rosenberg A., Lewis M., 2007, Structural analysis of lac repressor bound to allosteric effectors., J Mol Biol. 370(4):609-19

 [2] Flashner Y., Gralla JD., 1988, Dual mechanism of repression at a distance in the lac operon., Proc Natl Acad Sci U S A. 85(23):8968-72

 [3] Jimenez CR., Li KW., Smit AB., Janse C., 2005, Auto-inhibitory control of peptidergic molluscan neurons and reproductive senescence., Neurobiol Aging NIL

 [4] Oehler S., Eismann ER., Kramer H., Muller-Hill B., 1990, The three operators of the lac operon cooperate in repression., EMBO J. 9(4):973-9

 [5] Hoare AM., McLeish A., Thompson H., Alexander-Williams J., 1978, Selection of patients for bile diversion surgery: use of bile acid measurement in fasting gastric aspirates., Gut. 19(3):163-5

 [6] Lewis M., 2005, The lac repressor., C R Biol. 328(6):521-48

 [7] Rastinejad F., Artz P., Lu P., 1993, Origin of the asymmetrical contact between lac repressor and lac operator DNA., J Mol Biol. 233(3):389-99

 [8] Hudson JM., Fried MG., 1990, Co-operative interactions between the catabolite gene activator protein and the lac repressor at the lactose promoter., J Mol Biol. 214(2):381-96

 [9] Vossen KM., Stickle DF., Fried MG., 1996, The mechanism of CAP-lac repressor binding cooperativity at the E. coli lactose promoter., J Mol Biol. 255(1):44-54

 [10] Sanchez A., Osborne ML., Friedman LJ., Kondev J., Gelles J., 2011, Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules., EMBO J. 30(19):3940-6

 [11] Fried MG., Hudson JM., 1996, DNA looping and lac repressor-CAP interaction., Science. 274(5294):1930-1: author reply 1931-2

 [12] Perros M., Steitz TA., 1996, DNA looping and lac repressor-CAP interaction., Science. 274(5294):1929-30: author reply 1931-2

 [13] Balaeff A., Mahadevan L., Schulten K., 2004, Structural basis for cooperative DNA binding by CAP and lac repressor., Structure. 12(1):123-32

 [14] Abo T., Inada T., Ogawa K., Aiba H., 2000, SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon., EMBO J. 19(14):3762-9

 [15] Semsey S., Jauffred L., Csiszovszki Z., Erdossy J., Steger V., Hansen S., Krishna S., 2013, The effect of LacI autoregulation on the performance of the lactose utilization system in Escherichia coli., Nucleic Acids Res. 41(13):6381-90

 [16] Mooney RA., Landick R., 2013, Building a better stop sign: understanding the signals that terminate transcription., Nat Methods. 10(7):618-9

 [17] Xu J., Liu S., Chen M., Ma J., Matthews KS., 2011, Altering residues N125 and D149 impacts sugar effector binding and allosteric parameters in Escherichia coli lactose repressor., Biochemistry. 50(42):9002-13

 [18] Hirsh AD., Lillian TD., Lionberger TA., Perkins NC., 2011, DNA modeling reveals an extended lac repressor conformation in classic in vitro binding assays., Biophys J. 101(3):718-26

 [19] Becker NA., Maher LJ., 2015, High-resolution mapping of architectural DNA binding protein facilitation of a DNA repression loop in Escherichia coli., Proc Natl Acad Sci U S A. 112(23):7177-82

 [20] Lewis M., Chang G., Horton NC., Kercher MA., Pace HC., Schumacher MA., Brennan RG., Lu P., 1996, Crystal structure of the lactose operon repressor and its complexes with DNA and inducer., Science. 271(5253):1247-54

 [21] Hammar P., Leroy P., Mahmutovic A., Marklund EG., Berg OG., Elf J., 2012, The lac repressor displays facilitated diffusion in living cells., Science. 336(6088):1595-8

 [22] Fulcrand G., Chapagain P., Dunlap D., Leng F., 2016, Direct observation of a 91 bp LacI-mediated, negatively supercoiled DNA loop by atomic force microscope., FEBS Lett. 590(5):613-8

 [23] Fulcrand G., Dages S., Zhi X., Chapagain P., Gerstman BS., Dunlap D., Leng F., 2016, DNA supercoiling, a critical signal regulating the basal expression of the lac operon in Escherichia coli., Sci Rep. 6:19243



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