In cell biology, catabolite activator protein (CAP), which is also known as cAMP receptor protein (CRP), is a trans-acting transcriptional activator in bacteria that effectively catalyzes the initiation of DNA transcription by interacting with RNA polymerase in a way that causes the DNA to bend. [1]
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CAP's name reflects the protein's ability to affect transcription of genes involved in many catabolic pathways. For example, when the amount of glucose transported into a cell is low, a cascade of events results in the increase of cAMP levels in the cell's cytosol, and this increase in cAMP levels is sensed by CAP, which goes on to activate the transcription of many other catabolic genes.
CAP exists as a homodimer in solution, and it is bound to by two cyclic AMP (cAMP) ligand molecules with negative cooperativity. By increasing CAP's affinity for DNA, cAMP functions as an allosteric effector.
With its cyclic-AMP ligand, CAP binds a DNA region upstream from the site at which RNA polymerase binds and activates transcription through protein-protein interactions with RNA polymerase's α-subunit. This protein-protein interaction both catalyzes the formation of the RNAP-promoter closed complex and isomerizes the RNAP-promoter complex to the open conformation.
CAP has a characteristic helix-turn-helix motif structure that allows it to bind to successive major grooves on DNA. The two helices are reinforcing, each causing a 43° turn in the structure, with an overall 94° degree turn in the DNA. [2] Each subunit of CAP is composed of a ligand-binding domain at the N-terminus (CAPN, residues 1–138) and a DNA-binding domain at the C-terminus (DBD, residues 139–209). [3] [4]
