Diphtheria toxin is an
exotoxinAn exotoxin is a toxin excreted by a microrganism, including bacteria, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host...
secreted by
Corynebacterium diphtheriaeCorynebacterium diphtheriae is a pathogenic bacterium that causes diphtheria. It is also known as the Klebs-Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs and Friedrich Löffler .-Classification:Four subspecies are recognized: C. diphtheriae mitischodis,...
, the
pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
bacteriumThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
that causes
diphtheriaDiphtheria is an upper respiratory tract illness characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity. A milder form of diphtheria can be restricted to the skin...
.
Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two
subunitsIn structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally-occurring proteins and enzymes are multimeric...
linked by disulfide bridges. Binding to the cell surface of the less stable of these two subunits allows the more stable part of the protein to penetrate the
host cellIn biology, a host is an organism that harbors a parasite , or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
.
It catalyzes the
ADP-ribosylationADP Ribosylation Factors are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally...
of eukaryotic
elongation factorElongation factors are a set of proteins that facilitate the events of translational elongation, the steps in protein synthesis from the formation of the first peptide bond to the formation of the last one.Elongation is the most rapid step in translation:...
-2 (eEF2), inactivating this protein.
Diphtheria toxin is an
exotoxinAn exotoxin is a toxin excreted by a microrganism, including bacteria, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host...
secreted by
Corynebacterium diphtheriaeCorynebacterium diphtheriae is a pathogenic bacterium that causes diphtheria. It is also known as the Klebs-Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs and Friedrich Löffler .-Classification:Four subspecies are recognized: C. diphtheriae mitischodis,...
, the
pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
bacteriumThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
that causes
diphtheriaDiphtheria is an upper respiratory tract illness characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity. A milder form of diphtheria can be restricted to the skin...
.
Structure
Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two
subunitsIn structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally-occurring proteins and enzymes are multimeric...
linked by disulfide bridges. Binding to the cell surface of the less stable of these two subunits allows the more stable part of the protein to penetrate the
host cellIn biology, a host is an organism that harbors a parasite , or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
.
Mechanism
It catalyzes the
ADP-ribosylationADP Ribosylation Factors are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally...
of eukaryotic
elongation factorElongation factors are a set of proteins that facilitate the events of translational elongation, the steps in protein synthesis from the formation of the first peptide bond to the formation of the last one.Elongation is the most rapid step in translation:...
-2 (eEF2), inactivating this protein. It does so by ADP-ribosylating the unusual aminoacid
diphthamideDiphthamide is a modified histidine amino acid found in eukaryotic elongation factor 2 . It is ADP-ribosylated by diphtheria toxin, which renders the elongation factor inactive....
. In this way, it acts as a
RNA translationalTranslation is the first stage of protein biosynthesis . Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA...
inhibitor.
The
exotoxin AThe Pseudomonas exotoxin is an exotoxin produced by Pseudomonas aeruginosa.It acts at elongation factor-2. It has been investigated as a treatment for hepatitis B....
of
Pseudomonas aeruginosaPseudomonas aeruginosa is a common bacterium which can cause disease in animals and humans. It is found in soil, water, skin flora and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also with little oxygen, and has thus colonised many natural and...
uses a similar mechanism of action.
Lethal dose
Diphtheria toxin is extraordinarily potent. The
lethal doseA lethal dose is an indication of the lethality of a given substance or type of radiation. Because resistance varies from one individual to another, the 'lethal dose' represents a dose at which a given percentage of subjects will die.The most commonly-used lethality indicator is the...
for humans is about 0.1 μg of toxin per kg of bodyweight. A massive release of toxin into the body will likely cause lethal
necrosisNecrosis is the premature death of cells and living tissue. Necrosis is caused by external factors, such as infection, toxins , or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
of the
heartThe heart is a muscular organ found in all vertebrates that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
and
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
.