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LacI DNA-binding transcriptional repressor

Synonyms: LacI-allolactose, LacI
Summary:
The Lactose inhibitor," LacI, is a DNA-binding transcription factor that represses transcription of the operon involved in transport and catabolism of lactose [17, 19] In the absence of allolactose, LacI represses the lac operon by preventing open promoter complex formation for transcription [19] In this repression system, LacI binds to two operators, and formation of the repressor loop is critical [19] This repressor binds in tandem to inverted repeat sequences that are 21 nucleotides long and possess conserved motifs [19] 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 []. Induction occurs when the physiological inducer, allolactose, binds to the lac repressor, preventing it from binding to the operator [17, 19] Nonphysiological analogs, such as β-thiogalactosides, can function as inducers too [].
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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 [IE] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]
LacI-allolactose Non-Functional Allosteric Holo nd nd
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 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
  LacI repressor lacZp1 Sigma70 -82.0 -120.0 lacZ, lacY, lacA
aactcacattAATTGCGTTGCGCTCACTGCCcgctttccag
366415 366435 [HIBSCS], [SM] [13], [14], [15]
  LacI repressor lacZp1 Sigma70 11.0 -28.0 lacZ, lacY, lacA
tcctgtgtgaAATTGTTATCCGCTCACAATTccacacaaca
366323 366343 [HIBSCS], [SM] [13], [15], [16], [17], [18]
  LacI repressor lacZp1 Sigma70 412.0 373.0 lacZ, lacY, lacA
catcaacattAAATGTGAGCGAGTAACAACCcgtcggattc
365922 365942 [HIBSCS], [SM] [13], [15], [17]


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


Evidence    

 [IE] Inferred from experiment

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation



Reference(s)    

 [1] Beyreuther K., Adler K., Fanning E., Murray C., Klemm A., Geisler N., 1975, Amino-acid sequence of lac repressor from Escherichia coli. Isolation, sequence analysis and sequence assembly of tryptic peptides and cyanogen-bromide fragments., Eur J Biochem 59(2):491-509

 [2] Boelens R., Lamerichs RM., Rullmann JA., van Boom JH., Kaptein R., 1988, The interaction of lac repressor headpiece with its operator: an NMR view., Protein Seq Data Anal 1(6):487-98

 [3] Farabaugh PJ., 1978, Sequence of the lacI gene., Nature 274(5673):765-9

 [4] Ganem D., Miller JH., Files JG., Platt T., Weber K., 1973, Reinitiation of a lac repressor fragment at a codon other than AUG., Proc Natl Acad Sci U S A 70(11):3165-9

 [5] Gordon AJ., Burns PA., Fix DF., Yatagai F., Allen FL., Horsfall MJ., Halliday JA., Gray J., Bernelot-Moens C., Glickman BW., 1988, Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein., J Mol Biol 200(2):239-51

 [6] Jacob F., Monod J., 1961, Genetic regulatory mechanisms in the synthesis of proteins., J Mol Biol 3:318-56

 [7] Kisters-Woike B., Lehming N., Sartorius J., von Wilcken-Bergmann B., Muller-Hill B., 1991, A model of the lac repressor-operator complex based on physical and genetic data., Eur J Biochem 198(2):411-9

 [8] Lamerichs RM., Boelens R., van der Marel GA., van Boom JH., Kaptein R., Buck F., Fera B., Ruterjans H., 1989, H NMR study of a complex between the lac repressor headpiece and a 22 base pair symmetric lac operator., Biochemistry 28(7):2985-91

 [9] Lehming N., Sartorius J., Kisters-Woike B., von Wilcken-Bergmann B., Muller-Hill B., 1990, Mutant lac repressors with new specificities hint at rules for protein--DNA recognition., EMBO J 9(3):615-21

 [10] Markiewicz P., Kleina LG., Cruz C., Ehret S., Miller JH., 1994, Genetic studies of the lac repressor. XIV. Analysis of 4000 altered Escherichia coli lac repressors reveals essential and non-essential residues, as well as "spacers" which do not require a specific sequence., J Mol Biol 240(5):421-33

 [11] Pardee AB., Prestidge LS., 1959, On the nature of the repressor of beta-galactosidase synthesis in Escherichia coli., Biochim Biophys Acta 36:545-7

 [12] Platt T., Files JG., Weber K., 1973, Lac repressor. Specific proteolytic destruction of the NH 2 -terminal region and loss of the deoxyribonucleic acid-binding activity., J Biol Chem 248(1):110-21

 [13] 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

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

 [15] 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

 [16] 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

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

 [18] 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

 [19] 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



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