cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...

, catabolite activator protein (CAP), which is also known as cAMP receptor protein (CRP), is a

trans-acting In the field of molecular biology, ''trans''-acting (''trans''-regulatory, ''trans''-regulation), in general, means "acting from a different molecule" (''i.e.'', intermolecular). It may be considered the opposite of ''cis''-acting (''cis''-regula ...

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 ...

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

that effectively catalyzes the initiation of

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

transcription by interacting with

RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template. Using the e ...

in a way that causes the DNA to bend. CAP's name reflects the protein's ability to affect transcription of genes involved in many

catabolic Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipi ...

pathways. For example, when the amount of

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

transported into a cell is low, a cascade of events results in the increase of cAMP levels in the cell's

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 ...

, 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 biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins ...

in solution, and it is bound to by two cyclic AMP (cAMP)

ligand In coordination chemistry, a ligand is an ion or molecule with a 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 el ...

molecules with negative cooperativity. 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 Pa ...

for

, cyclic AMP 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 Helix-turn-helix is a DNA-binding domain (DBD). The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two alpha helix, α helices, joined by a short strand of amino acids, that bind to the majo ...

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. Each subunit of CAP is composed of a

-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 amin ...

(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, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

(DBD, residues 139–209).

CAP's role in the catabolism of saccharides

One example of the role of CAP is its criticality in activating the ability of '' E. coli'' to metabolize

lactose Lactose is a disaccharide composed of galactose and glucose and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from (Genitive case, gen. ), the Latin word for milk, plus the suffix ''-o ...

. The cAMP-CAP complex allows RNA polymerase to bind to the ''lac'' operon and transcribe its genes, which encode the proteins required for breaking down lactose into glucose and

galactose Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...

. Regulation of the ''lac'' operon is vital for ''E. coli'' because glucose is more easily metabolized—and is therefore a more economical source of

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

—than lactose. So the cell "prefers" glucose, and its presence causes the ''lac'' operon to be repressed regardless how much lactose may be available. Such conditional turning off of genes for metabolizing less-preferred substances, known as catabolite repression, is common in bacteria, and CAP plays an important role in it. Besides its function in activating the ''lac'' operon, CAP has a similar role in the Mal regulon, controlling the expression of ''malT'', a gene critical in the uptake and metabolism of

maltodextrin Maltodextrin is a name shared by two different families of chemicals. Both families are glucose polymers (also called ''dextrose polymers'' or ''Dextrin, dextrins''), but have little chemical or nutritional similarity. The digestible maltodextr ...

References

External links

* DNA {{Cell-biology-stub