Regulation by cAMP-CRP

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Many microbes have a regulatory process called "catabolite repression". During growth on a preferred carbon source, transcription of genes involved in the catabolism of other carbon sources is prevented. In Enterobacteriaciae (such as E. coli), this process is mediated by the CRP protein. (CRP stands for "Catabolite regulation protein". This protein is also sometimes called CAP for "Catabolite Activator Protein".) The presence or absence of glucose determines the concentration of cAMP, the small molecule effector that determines the activity of CRP.

cAMP-CRP activates expression of many genes. cAMP-CRP activates transcription by binding to specific sites on the DNA where it directly interacts with RNA Polymerase. (cAMP-CRP complex also represses expression of a few genes where the binding site overlaps with the promoter.) cAMP-CRP binding sites can be located approximately 61 bp upstream of the promoter (Class I CRP-binding sites), 41 bp upstream of the promoter (Class II CRP-binding sites), or >90 bp upstream of the promoter (Class III CRP-binding sites). The cAMP-CRP consensus binding site is:

TGTGA - N6 - TCACA

There are many variations on this sequence that influence the affinity of cAMP-CRP binding to different sites, resulting in a hierarchy of cAMP-CRP activation of different operons. The relative affinity of cAMP-CRP for binding sites on the E. coli chromosome varies over 50-fold. The crystal structure of the cAMP-CRP complex bound to DNA is shown below (from the EPASy Molecular Biology server).

How is the concentration of cAMP determined by the availability of glucose?

When glucose is transported, the phosphate group from enzyme IIIglc-P is rapidly transferred to glucose so the concentration of enzyme IIIglc-P remains low. Under these conditions adenylate cyclase has low enzymatic activity, thus the [cAMP] remains low.

When glucose is absent, the concentration of enzyme IIIglc remains high. Enzyme IIIglc-P activates adenylate cyclase to produce cAMP. Thus, the [cAMP] increases in the absence of glucose.

There are also other mechanisms of catabolite repression in Enterobacteriaceae. Furthermore, many microbes that demonstrate catabolite repression do not use cAMP for this process.

SOME USEFUL REFERENCES ON CATABOLITE REPRESSION:


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Last modified October 26, 2005