eTopic 10.1 Interactions between RNA Polymerase CRP and CRP-Dependent Promoters

Cyclic AMP receptor protein (CRP) is an important transcriptional regulator in many Gram-negative bacteria. This protein controls the expression of many different genes in the cell in response to the cellular level of cAMP. Interaction of cAMP-CRP with RNA polymerase at the lac promoter and at the promoters of several other genes typically occurs at the C-terminal domain of the RNA polymerase alpha subunit (Text Fig. 10.9, class I promoters). With some other promoters affected by cAMP, CRP can also engage the N-terminal domain of the alpha subunit (Fig. 1, class II promoters). These protein-protein interactions stimulate RNA polymerase bound at the promoter to initiate transcription.

Three classes of promoters require CRP activation, with each class differing in where CRP binds. CRP binds class I, II, and III promoters at -60 bp, -41 bp, and -90 bp, respectively, from the start of transcription. The differences in binding location reflect the amount of “encouragement” a particular RNA polymerase–-promoter complex must receive from CRP to change from a closed promoter complex to the open promoter complex necessary for transcription (see Section 8.2).

Class I promoters (lacP) were discussed in Section 10. In Class II promoters, however, where CRP binding overlaps the –35 promoter region (Fig. 1), CRP also touches the N terminus of the alpha subunit, which, along with contact of CRP at the C terminus, is needed to stimulate transcription. CRP essentially strengthens a weak –35 site. Transcription of class III promoters requires activator proteins in addition to CRP (see the discussion of the arabinose operon in Section 10.3).


Figure 1  The CRP-binding site on class II promoters at -41 bp, overlaps the RNA polymerase–binding site, allowing CRP to interact with the C-terminal and N-terminal domains of the alpha subunit. CRP binds the third class of promoter (not shown) at -90 bp. Source: Adapted from Moat et al. 2002. Microbial Physiology, 4th ed.