Lac operator repressor

Fried, M and Crothers, D. M. (1981) Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide-gel electrophoresis. Nucleic Acids Res 9, 6505-6525... 

Riggs, A.D., Suzuki, H., Bourgeois, S. (1970) Lac-Repressor-Operator Interactions I. Equilibrium Studies,/. Mol. Biol. 48, 67-83. 

Eon S., Culard F, Sy D., Charlier M., Spotheim-Maurizot M., Radiation disrupts protein-DNA complexes through damage to the protein.The lac repressor-operator system, Radiat. Res., 2001, 156,110-117. 

Bromo-2 -deoxyuri- Complementary sites dine-substituted lac on lac repressor operator From various aromatic chromophores Suggest intermolecular cross-linking 133... 

Riggs, A. D., Bourgeois, S. Cohn, M. (1970). The lac repressor-operator interaction III Kinetic studies. Journal of Molecular Biology, S3,401-17. 

Jobe, A., Bourgeois, S. Lac repressor-operator interaction. VI. The natural inducer of the lac operon. J. molec. Biol. 69, 397-408 (1972). 

More than 30 years ago Jacob and Monod introduced the Escherichia coli lac operon as a model for gene regulation. The lac repressor molecule functions as a switch, regulated by inducer molecules, which controls the synthesis of enzymes necessary for E. coli to use lactose as an energy source. In the absence of lactose the repressor binds tightly to the operator DNA preventing the synthesis of these enzymes. Conversely when lactose is present, the repressor dissociates from the operator, allowing transcription of the operon. 

Boelens, R., et al. Complex of lac repressor headpiece with a 14 base-pair lac operator fragment studied by two-dimensional nuclear magnetic resonance. /. Mol. Biol. 193 213-216, 1987. 

F. Culard, M. Schnarr, and J. C. Maurizot, Interaction between the lac operator and the lac repressor headpiece Fluorescence and circular dichroism studies, EMBO J. 1, 1405-1409 (1982). 

Ha et al. [18] have measured the equilibrium quotients for the formation of a complex between the lac repressor protein and a symmetric operator sequence of DNA as a function of temperature. Their results are given below. (The standard state is 1 mol dm. )... 

The lac repressor (encoded by the i gene), vdiidi binds to a DNA sequence called the operator... 

Pace, H. C., Lu, P and Lewis, M. (1990). lac repressor crystalhzation of intact tetramer and its complexes with inducer and operator DNA. Proc. Natl. Acad. Sci. USA 87,1870-1873. 

Fig. 1.19. Tetramerization of the Lac repressor and loop formation of the DNA. The Lac repressor from E. coli binds as a dimer to the two-fold symmetric operator seqnence, whereby each of the monomers contacts a half-site of a recognition sequence. The Lac operon of E. coli possesses three operator sequences Of, 02 and 03, aU three of which are required for complete repression. Of and 03 are separated by 93 bp, and only these two sequences are displayed in the figure above. Between Of and 03 is a binding site for the CAP protein and the contact surface for the RNA polymerase. The Lac repressor acts as a tetramer. It is therefore assumed that two dimers of the repressor associate to form the active tetramer, whereby one of the two dimers is bound to 03, the other dimer binds to Of. The intervening DNA forms a so-caUed repression loop. After Lewis et al., 1996.

Despite this elaborate binding complex, repression is not absolute. Binding of the Lac repressor reduces the rate of transcription initiation by a factor of 10s. If the 02 and 03 sites are eliminated by deletion or mutation, the binding of repressor to CL alone reduces transcription by a factor of about 102. Even in the repressed state, each cell has a few molecules of /3-galactosidase and galactoside permease, presumably synthesized on the rare occasions when the repressor transiently dissociates from the operators. This basal level of transcription is essential to operon regulation. 

In bacteria, genes that encode products with interdependent functions are often clustered in an operon, a single transcriptional unit. Transcription of the genes is generally blocked by binding of a specific repressor protein at a DNA site called an operator. Dissociation of the repressor from the operator is mediated by a specific small molecule, an inducer. These principles were first elucidated in studies of the lactose (lac) operon. The Lac repressor dissociates from the lac operator when the repressor binds to its inducer, allolactose. 

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