CAMP-CRP

Three states of the lac operon showing that lac mRNA is made only if cAMP-CRP is present and repressor is absent. 

Sogaard-Andersen L., Valentin-Hansen P. (1993) Protein-protein interactions in gene regulation The cAMP-CRP complex sets the specificity of a second DNA-binding protein, the CytR repressor. Cell 75 557. 

Regulation - The araC gene encodes a regulatory protein that binds to arabinose, the inducer of the operon. Binding of the AraC - arabinose complex at a site called aral activates transcription of the arabinose operon, but only when the cAMP - CRP complex (see here) is bound at an adjacent site. Thus, whereas the lac operon requires one protein to be bound and one to be dissociated for maximal transcription, the arabinose operon requires two proteins to be bound at adjacent sites. 

Transcription from the SI promoter depends on the presence of the cAMP - CRP complex (see here). 

Fig. 16.7. Catabolite repression of stimulatory proteins. The lac operon is used as an example. A. The inducer allolactose (a metabolite of lactose) inactivates the repressor. However, because of the absence of the required coactivator, cAMP-CRP, no transcription occurs unless glucose is absent. B. In the absence of glucose, cAMP levels rise. cAMP forms a complex with the cAMP receptor protein (CRP). The binding of the cAMP-CRP complex to a regulatory region of the operon permits the binding of RNA polymerase to the promoter. Now the operon is transcribed, and the proteins are produced.

It seems that to alleviate this problem, promotors for catabolic operons in E. coli form a hierarchy with respect to their affinity for RNA polymerase those for rapidly-metabolized carbon sources being the strongest and those for poor carbon sources the weakest. Moreover, the weaker the promoter, the higher the requirement for cyclic AMP and its receptor protein GRP for transcription to be initiated. Thus, powerful promoters are recognized by RNA polymerase in the virtual absence of cAMP/CRP and the operons transcribed, if induced. Promoters for poorer carbon sources which require cAMP/CRP for transcription can then be progressively switched on as the growth rate slows and the intracellular cAMP concentration rises until, the poorest carbon sources, which sustains the slowest growth rate (and hence... 

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