lacI

Summary

Gene Symbol: lacI
Description: lactose-inducible lac operon transcriptional repressor
Alias: ECK0342, JW0336
Species: Escherichia coli str. K-12 substr. MG1655
Products:     lacI

Top Publications

  1. Lewis M. The lac repressor. C R Biol. 2005;328:521-48 pubmed
    ..The structures of lac repressor, bound to its operator and inducer, have also been invaluable for interpreting a plethora of biochemical and genetic data. ..
  2. Saiz L, Rubi J, Vilar J. Inferring the in vivo looping properties of DNA. Proc Natl Acad Sci U S A. 2005;102:17642-5 pubmed
    ..These unexpected results can confer to the physical properties of DNA a more prominent role at shaping the properties of gene regulation than previously thought. ..
  3. Zhang Y, McEwen A, Crothers D, Levene S. Analysis of in-vivo LacR-mediated gene repression based on the mechanics of DNA looping. PLoS ONE. 2006;1:e136 pubmed
    ....
  4. van Hoek M, Hogeweg P. In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose. Biophys J. 2006;91:2833-43 pubmed
    ..Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers. ..
  5. Müller Hill B, Crapo L, Gilbert W. Mutants that make more lac repressor. Proc Natl Acad Sci U S A. 1968;59:1259-64 pubmed
  6. Perros M, Steitz T. DNA looping and lac repressor-CAP interaction. Science. 1996;274:1929-30; author reply 1931-2 pubmed
  7. Kalodimos C, Bonvin A, Salinas R, Wechselberger R, Boelens R, Kaptein R. Plasticity in protein-DNA recognition: lac repressor interacts with its natural operator 01 through alternative conformations of its DNA-binding domain. EMBO J. 2002;21:2866-76 pubmed
    ....
  8. Kopke Salinas R, Folkers G, Bonvin A, Das D, Boelens R, Kaptein R. Altered specificity in DNA binding by the lac repressor: a mutant lac headpiece that mimics the gal repressor. Chembiochem. 2005;6:1628-37 pubmed
    ....
  9. Guido N, Wang X, Adalsteinsson D, McMillen D, Hasty J, Cantor C, et al. A bottom-up approach to gene regulation. Nature. 2006;439:856-60 pubmed
    ..This work shows that the properties of regulatory subsystems can be used to predict the behaviour of larger, more complex regulatory networks, and that this bottom-up approach can provide insights into gene regulation. ..
  10. Santillan M. Bistable behavior in a model of the lac operon in Escherichia coli with variable growth rate. Biophys J. 2008;94:2065-81 pubmed
    ..The results are discussed in regard to the bistable behavior of the lactose operon. Special attention is paid to the effect that a variable growth rate has on the system dynamics. ..

Detail Information

Publications62

  1. Lewis M. The lac repressor. C R Biol. 2005;328:521-48 pubmed
    ..The structures of lac repressor, bound to its operator and inducer, have also been invaluable for interpreting a plethora of biochemical and genetic data. ..
  2. Saiz L, Rubi J, Vilar J. Inferring the in vivo looping properties of DNA. Proc Natl Acad Sci U S A. 2005;102:17642-5 pubmed
    ..These unexpected results can confer to the physical properties of DNA a more prominent role at shaping the properties of gene regulation than previously thought. ..
  3. Zhang Y, McEwen A, Crothers D, Levene S. Analysis of in-vivo LacR-mediated gene repression based on the mechanics of DNA looping. PLoS ONE. 2006;1:e136 pubmed
    ....
  4. van Hoek M, Hogeweg P. In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose. Biophys J. 2006;91:2833-43 pubmed
    ..Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers. ..
  5. Müller Hill B, Crapo L, Gilbert W. Mutants that make more lac repressor. Proc Natl Acad Sci U S A. 1968;59:1259-64 pubmed
  6. Perros M, Steitz T. DNA looping and lac repressor-CAP interaction. Science. 1996;274:1929-30; author reply 1931-2 pubmed
  7. Kalodimos C, Bonvin A, Salinas R, Wechselberger R, Boelens R, Kaptein R. Plasticity in protein-DNA recognition: lac repressor interacts with its natural operator 01 through alternative conformations of its DNA-binding domain. EMBO J. 2002;21:2866-76 pubmed
    ....
  8. Kopke Salinas R, Folkers G, Bonvin A, Das D, Boelens R, Kaptein R. Altered specificity in DNA binding by the lac repressor: a mutant lac headpiece that mimics the gal repressor. Chembiochem. 2005;6:1628-37 pubmed
    ....
  9. Guido N, Wang X, Adalsteinsson D, McMillen D, Hasty J, Cantor C, et al. A bottom-up approach to gene regulation. Nature. 2006;439:856-60 pubmed
    ..This work shows that the properties of regulatory subsystems can be used to predict the behaviour of larger, more complex regulatory networks, and that this bottom-up approach can provide insights into gene regulation. ..
  10. Santillan M. Bistable behavior in a model of the lac operon in Escherichia coli with variable growth rate. Biophys J. 2008;94:2065-81 pubmed
    ..The results are discussed in regard to the bistable behavior of the lactose operon. Special attention is paid to the effect that a variable growth rate has on the system dynamics. ..
  11. Vilar J, Guet C, Leibler S. Modeling network dynamics: the lac operon, a case study. J Cell Biol. 2003;161:471-6 pubmed
    ..We integrate three different levels of description (molecular, cellular, and that of cell population) into a single model, which seems to capture many experimental aspects of the system. ..
  12. Müller Hill B. The function of auxiliary operators. Mol Microbiol. 1998;29:13-8 pubmed
    ..For this purpose, a strategy is used over and over again. It is called increase in local concentration. How Escherichia coli uses this strategy efficiently is discussed. ..
  13. van Hoek M, Hogeweg P. The effect of stochasticity on the lac operon: an evolutionary perspective. PLoS Comput Biol. 2007;3:e111 pubmed
    ..Moreover, we demonstrate that in silico evolution in a quantitative model, by mutating the parameters of interest, is a promising way to unravel the functional properties of biological systems. ..
  14. Swigon D, Coleman B, Olson W. Modeling the Lac repressor-operator assembly: the influence of DNA looping on Lac repressor conformation. Proc Natl Acad Sci U S A. 2006;103:9879-84 pubmed
    ....
  15. Romanuka J, Folkers G, Biris N, Tishchenko E, Wienk H, Bonvin A, et al. Specificity and affinity of Lac repressor for the auxiliary operators O2 and O3 are explained by the structures of their protein-DNA complexes. J Mol Biol. 2009;390:478-89 pubmed publisher
    ....
  16. Yildirim N, Mackey M. Feedback regulation in the lactose operon: a mathematical modeling study and comparison with experimental data. Biophys J. 2003;84:2841-51 pubmed
    ....
  17. Ozbudak E, Thattai M, Lim H, Shraiman B, van Oudenaarden A. Multistability in the lactose utilization network of Escherichia coli. Nature. 2004;427:737-40 pubmed
    ..The phase diagram thus serves as a sensitive probe of molecular interactions and as a powerful tool for rational network design. ..
  18. Abo T, Inada T, Ogawa K, Aiba H. SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon. EMBO J. 2000;19:3762-9 pubmed
    ..COLI: cells. More specifically, we report that the lacI mRNA encoding Lac repressor (LacI) is a specific natural target for trans-translation...
  19. Lewis M, Chang G, Horton N, Kercher M, Pace H, Schumacher M, et al. Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science. 1996;271:1247-54 pubmed
    ..Its key component is the lac repressor, a product of the lacI gene...
  20. Sartorius J, Lehming N, Kisters B, von Wilcken Bergmann B, Müller Hill B. lac repressor mutants with double or triple exchanges in the recognition helix bind specifically to lac operator variants with multiple exchanges. EMBO J. 1989;8:1265-70 pubmed
    ..Mutations of residues 1 and 2 may be combined with a mutation of residue 6. The resulting mutant protein binds specifically to an operator variant with three symmetric exchanges in base pairs 4, 5 and 6. ..
  21. Vossen K, Stickle D, Fried M. The mechanism of CAP-lac repressor binding cooperativity at the E. coli lactose promoter. J Mol Biol. 1996;255:44-54 pubmed
    ..reduced by the removal of DNA located upstream of the CAP binding site or by substitution of the dimeric lacI-18 mutant repressor for the wild-type tetrameric protein...
  22. Gillard N, Goffinont S, Buré C, Davidkova M, Maurizot J, Cadene M, et al. Radiation-induced oxidative damage to the DNA-binding domain of the lactose repressor. Biochem J. 2007;403:463-72 pubmed
    ..The loss of repressor function is thus correlated with chemical modifications and conformational changes of the headpiece. ..
  23. Gordon A, Burns P, Fix D, Yatagai F, Allen F, Horsfall M, et al. Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein. J Mol Biol. 1988;200:239-51 pubmed
    ..We have been using the lacI gene-repressor protein system to study the mutational specificity of spontaneous and induced mutation...
  24. von Hippel P. Biochemistry. Completing the view of transcriptional regulation. Science. 2004;305:350-2 pubmed
  25. Steege D. 5'-Terminal nucleotide sequence of Escherichia coli lactose repressor mRNA: features of translational initiation and reinitiation sites. Proc Natl Acad Sci U S A. 1977;74:4163-7 pubmed
    ..Third, the formation of stable secondary structures predicted for the untranslated I mRNA beyond chain-terminating nonsense mutations may prevent ribosome access to some potential reinitiation sites. ..
  26. Rosenberg S, Hastings P. Adaptive point mutation and adaptive amplification pathways in the Escherichia coli Lac system: stress responses producing genetic change. J Bacteriol. 2004;186:4838-43 pubmed
  27. Bharatan S, Reddy M, Gowrishankar J. Distinct signatures for mutator sensitivity of lacZ reversions and for the spectrum of lacI/lacO forward mutations on the chromosome of nondividing Escherichia coli. Genetics. 2004;166:681-92 pubmed
    ..Escherichia coli, first to eliminate all growth-associated chromosomal reversions in lacZ or forward mutations in lacI/lacO by incubation at the restrictive temperature and subsequently to recover (as papillae) spontaneous mutations ..
  28. Goffinont S, Davidkova M, Spotheim Maurizot M. Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor. Biochem Biophys Res Commun. 2009;386:300-4 pubmed publisher
    ..The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain. ..
  29. Semsey S, Jauffred L, Csiszovszki Z, Erdossy J, St ger V, Hansen S, et al. The effect of LacI autoregulation on the performance of the lactose utilization system in Escherichia coli. Nucleic Acids Res. 2013;41:6381-90 pubmed publisher
    ..Here we study the effect of autoregulation on intracellular LacI levels and also show that cAMP-CRP binding does not affect the efficiency of autoregulation...
  30. Balaeff A, Mahadevan L, Schulten K. Structural basis for cooperative DNA binding by CAP and lac repressor. Structure. 2004;12:123-32 pubmed
    ..Using the multiscale approach, we build an all-atom model of the ternary complex that suggests a series of further experimental investigations. ..
  31. Müller Hill B, Kania J. Lac repressor can be fused to beta-galactosidase. Nature. 1974;249:561-3 pubmed
  32. Daber R, Sharp K, Lewis M. One is not enough. J Mol Biol. 2009;392:1133-44 pubmed publisher
    ..Understanding how effector molecules alter the thermodynamic properties of the repressor is essential for establishing a detailed understanding of gene regulation. ..
  33. Xu J, Matthews K. Flexibility in the inducer binding region is crucial for allostery in the Escherichia coli lactose repressor. Biochemistry. 2009;48:4988-98 pubmed publisher
    Lactose repressor protein (LacI) utilizes an allosteric mechanism to regulate transcription in Escherichia coli, and the transition between inducer- and operator-bound states has been simulated by targeted molecular dynamics (TMD)...
  34. Mazier S, Villette S, Goffinont S, Renouard S, Maurizot J, Genest D, et al. Radiation damage to a DNA-binding protein. Combined circular dichroism and molecular dynamics simulation analysis. Radiat Res. 2008;170:604-12 pubmed publisher
    ..This conclusion should hold for all proteins containing radiosensitive amino acids in their DNA-binding site. ..
  35. Betz J. Cloning and characterization of several dominant-negative and tight-binding mutants of lac repressor. Gene. 1986;42:283-92 pubmed
    Using both general recombination and molecular cloning techniques, 13I-, I-d and Itb missense mutations in the lacI gene were transferred from F'lacIq episomes to ColE1 derivative plasmids...
  36. Borukhov S, Lee J. RNA polymerase structure and function at lac operon. C R Biol. 2005;328:576-87 pubmed
    ..by transcription activators, such as cyclic AMP-receptor protein, CRP, and negatively regulated by lac-repressor, LacI. In this review, we discuss the recent progress in structural and biochemical studies of RNAP and its binary and ..
  37. Blommel P, Becker K, Duvnjak P, Fox B. Enhanced bacterial protein expression during auto-induction obtained by alteration of lac repressor dosage and medium composition. Biotechnol Prog. 2007;23:585-98 pubmed
    ..coli is based on diauxic growth resulting from dynamic function of lac operon regulatory elements (lacO and LacI) in mixtures of glucose, glycerol, and lactose...
  38. Müller Hill B. Suppressible regulator constitutive mutants of the lactose system in Escherichia coli. J Mol Biol. 1966;15:374-6 pubmed
  39. Narang A. Effect of DNA looping on the induction kinetics of the lac operon. J Theor Biol. 2007;247:695-712 pubmed
    ..This suggests that repressor overexpression can induce bistability in systems, such as growth of E. coli on lactose, that are otherwise monostable. ..
  40. Shineberg B. Mutations partially inactivating the lactose repressor of Escherichia coli. J Bacteriol. 1974;119:500-7 pubmed
    ..An explanation is proposed for the apparent sensitivity of this repressor function to partial inactivation as the result of amino acid substitutions. ..
  41. Langridge J. Mutations conferring quantitative and qualitative increases in beta-galactosidase activity in Escherichia coli. Mol Gen Genet. 1969;105:74-83 pubmed
  42. Bell C, Barry J, Matthews K, Lewis M. Structure of a variant of lac repressor with increased thermostability and decreased affinity for operator. J Mol Biol. 2001;313:99-109 pubmed
    ....
  43. Sartorius J, Lehming N, Kisters Woike B, von Wilcken Bergmann B, Müller Hill B. The roles of residues 5 and 9 of the recognition helix of Lac repressor in lac operator binding. J Mol Biol. 1991;218:313-21 pubmed
    ..They further suggest that residue 9 of the recognition helix (asparagine 25) interacts non-specifically with a phosphate of the DNA backbone, possibly between base-pairs 2 and 3. ..
  44. Kepes A. Sequential transcription and translation in the lactose operon of Escherichia coli. Biochim Biophys Acta. 1967;138:107-23 pubmed
  45. Brickner J, Walter P. Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS Biol. 2004;2:e342 pubmed
    ..Gene recruitment to the nuclear periphery, therefore, is a dynamic process and appears to play an important regulatory role. ..
  46. Tomshine J, Kaznessis Y. Optimization of a stochastically simulated gene network model via simulated annealing. Biophys J. 2006;91:3196-205 pubmed
    ..The repressilator is optimized to give oscillations of an arbitrary specified period. These optimized designs may then provide a starting-point for the selection of genetic components needed to realize an in vivo system. ..
  47. Xu J, Liu S, Chen M, Ma J, Matthews K. Altering residues N125 and D149 impacts sugar effector binding and allosteric parameters in Escherichia coli lactose repressor. Biochemistry. 2011;50:9002-13 pubmed publisher
    Lactose repressor protein (LacI), a negative transcriptional regulator in Escherichia coli, relies on an allosteric conformational change for its function...
  48. Zurla C, Samuely T, Bertoni G, Valle F, Dietler G, Finzi L, et al. Integration host factor alters LacI-induced DNA looping. Biophys Chem. 2007;128:245-52 pubmed
    ..coli. In single molecule experiments, we show that both specific bending and non-specific compaction alter LacI-mediated looping of DNA...
  49. Farabaugh P. Sequence of the lacI gene. Nature. 1978;274:765-9 pubmed
    The structural gene for the lac repressor of Escherichia coli, the lacI gene has been sequenced. This 1,080 base pair region of the E. coli chromosome codes for the lac repressor protein of 360 amino acids...
  50. Morgan M, Okamoto K, Kahn J, English D. Single-molecule spectroscopic determination of lac repressor-DNA loop conformation. Biophys J. 2005;89:2588-96 pubmed
    The Escherichia coli lactose repressor protein (LacI) provides a classic model for understanding protein-induced DNA looping. LacI has a C-terminal four-helix bundle tetramerization domain that may act as a flexible hinge...
  51. Santillan M, Mackey M. Quantitative approaches to the study of bistability in the lac operon of Escherichia coli. J R Soc Interface. 2008;5 Suppl 1:S29-39 pubmed publisher
    ..A review of the literature in which this bistable phenomenon has been studied from a mathematical modelling viewpoint is then given. We conclude with some brief remarks. ..
  52. Görke B, Reinhardt J, Rak B. Activity of Lac repressor anchored to the Escherichia coli inner membrane. Nucleic Acids Res. 2005;33:2504-11 pubmed
    ..Other mechanisms, like induction of a conformational change or masking of binding domains are required additionally. ..
  53. Spronk C, Bonvin A, Radha P, Melacini G, Boelens R, Kaptein R. The solution structure of Lac repressor headpiece 62 complexed to a symmetrical lac operator. Structure. 1999;7:1483-92 pubmed
    ..In addition, the structural features of the hinge region provide detailed insight into the protein-protein and protein-DNA interactions responsible for the high affinity of the repressor for operator DNA. ..
  54. Yudkin M. Catabolite repression of the lac operon. The contribution f trascriptional repression. Biochem J. 1969;114:307-11 pubmed
    ..It is also concluded that the extent of translational repression varies between strains. ..
  55. Stenberg K, Vihinen M. Crystal structure of a 1.6-hexanediol bound tetrameric form of Escherichia coli lac-repressor refined to 2.1 A resolution. Proteins. 2009;75:748-59 pubmed publisher
    We report the structure of a novel tetrameric form of the lactose repressor (LacI) protein from Escherichia coli refined to 2.1 A resolution. The tetramer is bound to 1...
  56. Choi P, Cai L, Frieda K, Xie X. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science. 2008;322:442-6 pubmed publisher
    ..Hence, a stochastic single-molecule event determines a cell's phenotype. ..
  57. Stoebel D. Lack of evidence for horizontal transfer of the lac operon into Escherichia coli. Mol Biol Evol. 2005;22:683-90 pubmed
    ....
  58. Spronk C, Folkers G, Noordman A, Wechselberger R, van den Brink N, Boelens R, et al. Hinge-helix formation and DNA bending in various lac repressor-operator complexes. EMBO J. 1999;18:6472-80 pubmed
    ....
  59. Miller J. Structure of a paradigm. Nat Struct Biol. 1996;3:310-2 pubmed
  60. Smith T, Sadler J. The nature of lactose operator constitive mutations. J Mol Biol. 1971;59:273-305 pubmed
  61. Mettetal J, Muzzey D, Pedraza J, Ozbudak E, van Oudenaarden A. Predicting stochastic gene expression dynamics in single cells. Proc Natl Acad Sci U S A. 2006;103:7304-9 pubmed
    ..Our results provide a proof of principle for the possibility of faithfully predicting dynamic population distributions from deterministic models supplemented by a stochastic component that captures the major noise sources. ..
  62. Saier M, Straud H, Massman L, Judice J, Newman M, Feucht B. Permease-specific mutations in Salmonella typhimurium and Escherichia coli that release the glycerol, maltose, melibiose, and lactose transport systems from regulation by the phosphoenolpyruvate:sugar phosphotransferase system. J Bacteriol. 1978;133:1358-67 pubmed
    ....