Lac repressor

The DNA binding ability of lac repressor bound with allolactose is inhibited due to allosteric regulation, thereby genes coding for proteins involved in lactose uptake and utilization can be expressed.

The lac repressor (LacI) operates by a helix-turn-helix motif in its DNA-binding domain, binding base-specifically to the major groove of the operator region of the lac operon, with base contacts also made by residues of symmetry-related alpha helices, the "hinge" helices, which bind deeply in the minor groove.

[1] This bound repressor can reduce transcription of the Lac proteins by occluding the RNA polymerase binding site or by prompting DNA looping.

[3] Isopropyl β-D-1-thiogalactopyranoside (IPTG) is a commonly used allolactose mimic which can be used to induce transcription of genes being regulated by lac repressor.

[11] These experiments also suggest that LacI slides over the O1 operator several times before binding, meaning that different DNA sequences can have different probabilities to be recognized at each encounter with the TF.

[12] The TF often leaves the sequence it is intended to regulate, but at a strong target site, it almost always make a very short journey before finding the way back again.

Annotated crystal structure of dimeric LacI . Two monomers (of four total) co-operate to bind each DNA operator sequence. Monomers (red and blue) contain DNA binding and core domains (labeled) which are connected by a linker (labeled). The C-terminal tetramerization helix is not shown. The repressor is shown in complex with operator DNA (gold) and ONPF (green), an anti-inducer ligand ( i.e. a stabilizer of DNA binding)
Tetrameric LacI binds two operator sequences and induces DNA looping. Two dimeric LacI functional subunits (red+blue and green+orange) each bind a DNA operator sequence (labeled). These two functional subunits are coupled at the tetramerization region (labeled); thus, tetrameric LacI binds two operator sequences. This allows tetrameric LacI to induce DNA looping.
Animation of binding and unbinding mechanism of a LacI dimer and its target DNA site.