Diphtheria toxin

• UniProt: P00588

The diphtheria toxin ( DT) is an exotoxin from Corynebacterium diphtheriae, the causative agent of diphtheria and inhibits protein synthesis in eukaryotes and archaea by blocking the translation during the elongation phase. The high molecular weight toxin is one of the lectins. The genetic information is contained in the phage β and only when the bacterium is infected by it, it may itself form the toxin.

Operation

The toxin is composed of two proteins, toxin A and toxin B, which are connected by disulphide bridges and binds selectively to the 80 S ribosomal of eukaryotic cells. Its mass is about 61 kDa. The penetration into the cell is subject to the same mechanism as for ricin: The B chain attaches itself to a receptor on the cell surface, wherein the toxin cleaves at a 21 kDa A- fragment and a 40 kDa fragment B, wherein the A fragment penetrates the cell. This mechanism has the diphtheria toxin with several other bacterial toxins together, it belongs to the group of AB toxins.

The aim of the enzymatic activity of the diphtheria toxin A is the elongation factor EF-2 which catalyzes the translation during protein synthesis in eukaryotes. EF-2 contains diphthamide, an unusual amino acid residue, with unknown function, which is formed from histidine. The A- fragment of the toxin catalyzes the covalent modification of this Diphthamids. In this case, ADP - Ribosylrest from NAD with loss of nicotinamide is transmitted to the diphthamide. One speaks of an ADP ribosylation. Wherein the diphtheria toxin inhibits the ability of the EF-2 to carry out the translation of the growing polypeptide chain. Protein synthesis stops, and this is the reason for the remarkable toxicity of the diphtheria toxin.

Similar toxins

Other toxins, coming from pathogens, consisting of two linked peptide chains, one of which binds to a receptor on the cell surface and then the other chain entry into the cell gives for example the cholera toxin, pertussis toxin ( pertussis toxin ) and anthrax toxin. However, the toxic mechanisms of these toxins are different. The identical mechanism of NAD-dependent ADP -ribosylation also uses the exotoxin A from Pseudomonas aeruginosa.