Daily Newsletter

November 12, 2013 - Lac Operon

The Lac operon has two levels of regulation. The first is through a repressor protein that binds to the operator of the operon. The repressor is constitutively expressed, and binds to the Lac Operon operator. When lactose is present, it binds to the repressor, thus changing the shape of the repressor protein; the repressor detaches from the operator, and transcription can occur.

There is a second regulation system for the Lac Operon, and it has to deal with the promoter and the CRP binding site. In the case of the Lac operon, the promoter is "weak". RNA polymerase does not readily bind to the promoter. To assist in binding RNA polymerase, there is an activator site (CRP binding site) that can be used to "enhance" the promoter (enhance the binding of RNA polymerase to the promoter).

CRP stands for cAMP Regulator Protein (it is also known as the Catabolite Activator Protein). CRP has a binding site for cAMP, and the protein is activated (turned on) when cAMP binds. The CRP-cAMP complex can bind to the CRP binding site, and alter the Lac Operon promoter, enhancing the binding of RNA Polymerase to the promoter.

As can be seen in the image above, CRP-cAMP leads to higher levels of operon transcription. But why this second regulatory system?

Remember that for this cell, glucose is the preferred carbohydrate and energy source (Escherichia coli is a chemoheterotrophic organism). The first regulatory system for the operon dealt with the presence/absence of Lactose (you only transcribe the operon when lactose is present). This second deals with the presence/absence of glucose. Glucose is the primary carbohydrate source, so as long as glucose is present, there is no need to transcribe pathways for secondary sugars.

In bacteria, the movement of glucose across the membrane (remember hexokinase?) inhibits the production of cAMP. If glucose transport slows dramatically or stops, Adenylate Cyclase begins making cAMP. So, while glucose available, there is little to no cAMP in the cell. When glucose is scarce, we see an increase in cellular levels of cAMP. For bacteria like E. coli, we can see cAMP as a starvation signal. The CRP-cAMP complex will bind around the bacterial DNA molecule, and activate numerous pathways for alternative carbohydrate utilization. As with the Lac Operon, these other pathways will only transcribe when the correct sugar is in the environment.

Daily Challenge

Explain in your own words the evolutionary advantage of having a two-stage regulatory system, as seen in the Lac Operon. In your discussion, explain why it is important to have secondary messages like cAMP act as signals for large environmental changes, such as starvation states.