In addition to the repressor, the lac-operon is regulated by another protein. This protein is known as the catabolite activator protein (CAP) or 3′, 5′-cycIic AMP (cAMP) receptor protein (CRP).
It has two DNA binding sites, just upstream of the promoter sequence. CAMP-CRP alone has a weak affinity for its site and so is RNA polymerase.
They bind to their respective sites simultaneously and subsequently enhance each other’s binding affinity. This type of binding is called cooperative binding.
The turning on or off of all the three structural genes depends chiefly on the presence or absence of an inducer (lactose) in the growth medium.
(a) In the Absence of Lactose:
In the absence of lactose in the medium, E. coli cells take recourse to another alternate energy source. The synthesis of all the three lactose metabolizing enzymes is inhibited. Under this circumstance, the repressor dimer / tetramer bind to the operator and prevent the binding of the RNA polymerase to the promoter. In its absence, the transcription process is inhibited.
(b) In the Presence of Lactose:
Conversely, when lactose is present in the medium, the repressor polypeptides of an active repressor bind to one each of lactose molecule.
This binding changes the conformational structure of the repressor protein, which can no longer bind to the operator. Under this circumstance, the RNA polymerase binds to the promoter and brings about the transcription of a poycistronic mRNA representing all the three structural genes. This poiycistronic mRNA like those of other prokaryotes is translated into three lactose catabolizing enzymes.