Pertussis toxin

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Pertussis toxin

Pertussis toxin (PT) is a protein-based AB₅-type

AB5 toxin

The AB5 toxins are six-component protein complexes secreted by a number of pathogenicity bacteria. All share a similar structure and mechanism for entering targeted host cells....
exotoxin

Exotoxin

An exotoxin is a toxin excreted by a microrganism, including bacterium, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism....
produced by the bacterium Bordetella pertussis
Bordetella pertussis

Bordetella pertussis is a Gram-negative, Aerobic_organism coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough....
, which causes whooping cough. PT is involved in the colonization of the respiratory tract

Respiratory tract

In humans the respiratory tract is the part of the anatomy that has to do with the process of Respiration .The respiratory tract is divided into 3 segments:...
and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments including hypertension, viral inhibition, and autoimmune inhibition.

s an exotoxin

Exotoxin

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Encyclopedia

Pertussis toxin (PT) is a protein-based AB₅-type

AB5 toxin

The AB5 toxins are six-component protein complexes secreted by a number of pathogenicity bacteria. All share a similar structure and mechanism for entering targeted host cells....
exotoxin

Exotoxin

Respiratory tract

Structure

PT is an exotoxin

Exotoxin

An exotoxin is a toxin excreted by a microrganism, including bacterium, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism....
with six subunits (named S1 through S5—each complex contains two copies of S4). The subunits are arranged in a A-B structure: the A component is enzymatically active

Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
and is formed from the S1 subunit, while the B component is the receptor

Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
-binding portion and is made up of subunits S2–S5. The subunits are encoded by ptx genes encoded on a large PT operon

Operon

An operon is a functioning unit of key nucleotide sequences of DNA including an operator , a common promoter, and one or more structural genes, which is controlled as a unit to produce mRNA , in the process of transcription by an RNA polymerase....
that also includes additional genes which encode Ptl proteins: Together these proteins form the PT secretion complex.

Mechanism of pathogenesis

PT is released from B. pertussis in an inactive form. When the B subunit binds to a cell membrane receptor

Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
, the A subunit (or protomer) becomes activated, perhaps through the action of glutathione

Glutathione

Glutathione is a tripeptide. It contains an unusual peptide linkage between the amino acid of cysteine and the carboxyl group of the glutamate side chain....
and ATP

Adenosine triphosphate

This article is about the chemical used by cells as an energy carrier. For other uses, see ATP .Adenosine-5'-triphosphate is a multifunctional nucleotide, and plays an important role in cell biology as a coenzyme that is the "molecule unit of currency" of intracellular energy transfer....
. PT catalyzes the ADP-ribosylation

ADP-ribosylation

ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis....
of the a subunits of the heterotrimeric G protein

G protein

G proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades.G proteins are so called because they function as "molecular switches," alternating between an inactive guanosine diphosphate and active guanosine triphosphate bound state, ultimately going on to regulate down...
s G_i, G_o, and G_t. This prevents the G proteins from interacting with G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the Cell and activate inside signal transductio...
s on the cell membrane

Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
, thus interfering with intracellular communication. Since the Ga subunits remain in their GDP-bound, inactive state, they are unable to inhibit adenylyl cyclase, thus keeping levels of adenylyl cyclase and cAMP elevated..