Catabolite activator protein
Catabolite Activator Protein (CAP; also known as cAMP receptor protein, CRP) is a trans-acting transcriptional activator that exists as a homodimer in solution, with each subunit comprising a ligand-binding domain at the N-terminus (CAPN, residues 1-138), which is also responsible for the dimerization of the protein, and a DNA-binding domain at the C-terminus (DBD, residues 139-209). Two cAMP (cyclic AMP) molecules bind dimeric CAP with negative cooperativity and function as allosteric effectors by increasing the protein's affinity for DNA. CAP binds a DNA region upstream from the DNA site for the RNAP II holoenzyme. CAP activates transcription through protein-protein interaction with the α-subunit C-terminal domain of the RNAP II holoenzyme. This protein-protein interaction is responsible for (i) catalyzing the formation of the RNAP-promoter closed complex; and (ii) isomerization of the RNAP-promoter closed complex to the RNAP-promoter open complex. Cytosolic cAMP levels rise when the amount of glucose transported into the cell is low.
CAP has a characteristic helix-turn-helix 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, so overall causing a 94° degree turn in the DNA.
This requirement reflects the greater simplicity with which glucose may be metabolized in comparison to lactose. The cell "prefers" glucose, and, if it is available, the lac operon is not activated, even when lactose is present. This is an effective way of integrating the two different signals.
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- Molecular Biology, 1st Edition (1999), by Robert F. Weaver. p. 193