Catabolite activator protein (CAP; also known as

cAMP receptor protein cAMP receptor protein (CRP; also known as catabolite activator protein, CAP) is a regulatory protein in bacteria. CRP protein binds cAMP, which causes a conformational change that allows CRP to bind tightly to a specific DNA site in the promot ...

, CRP) is a trans-acting

transcriptional activator A transcriptional activator is a protein (transcription factor) that increases transcription of a gene or set of genes. Activators are considered to have ''positive'' control over gene expression, as they function to promote gene transcription and ...

that exists as a

homodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...

in solution. Each subunit of CAP is composed of a

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

-binding domain at the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

(CAP^N, residues 1–138) and a

DNA-binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...

at the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

(DBD, residues 139–209). Two cAMP (

cyclic AMP Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal tra ...

) molecules bind dimeric CAP with negative cooperativity. Cyclic AMP functions as an allosteric effector by increasing CAP's

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for DNA. CAP binds a DNA region upstream from the DNA binding site of RNA Polymerase. CAP activates transcription through protein-protein interactions with the α-subunit of RNA Polymerase. This protein-protein interaction is responsible for (i) catalyzing the formation of the RNAP-promoter closed complex; and (ii) isomerization of the RNAP-promoter complex to the open conformation. CAP's interaction with RNA polymerase causes bending of the DNA near the transcription start site, thus effectively catalyzing the transcription initiation process. CAP's name is derived from its ability to affect transcription of genes involved in many catabolic pathways. For example, when the amount of glucose transported into the cell is low, a cascade of events results in the increase of

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

ic cAMP levels. This increase in cAMP levels is sensed by CAP, which goes on to activate the transcription of many other catabolic genes. CAP has a characteristic

helix-turn-helix Helix-turn-helix is a DNA-binding protein (DBP). The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two α helices, joined by a short strand of amino acids, that bind to the major groove of D ...

motif structure that allows it to bind to successive

major groove Major (commandant in certain jurisdictions) is a military rank of commissioned officer status, with corresponding ranks existing in many military forces throughout the world. When used unhyphenated and in conjunction with no other indicator ...

s on DNA. The two helices are reinforcing, each causing a 43° turn in the structure, with an overall 94° degree turn in the DNA. This interaction opens up the DNA molecule, allowing

RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...

to bind and

transcribe Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

the genes involved in lactose catabolism. cAMP-CAP is required for transcription activation of the ''lac'' operon. 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. This phenomenon is known as

catabolite repression Carbon catabolite repression, or simply catabolite repression, is an important part of global control system of various bacteria and other microorganisms. Catabolite repression allows microorganisms to adapt quickly to a preferred (rapidly metaboli ...

. CAP plays an important role in

, a well-known example of a

modulon In molecular genetics, a regulon is a group of genes that are gene regulation, regulated as a unit, generally controlled by the same regulatory gene that gene expression, expresses a protein acting as a repressor or activator (genetics), activator ...

and also plays a role in the Mal regulon.Molecular Biology, 1st Edition (1999), by Robert F. Weaver. p. 193

References

External links

* DNA {{Cell-biology-stub