Diphtheria toxin
| Diphtheria toxin (Corynephage β) | ||
|---|---|---|
|
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| Surface model according to PDB 1DDT . Chain A (enzyme) orange, chain B (transporter) light blue. | ||
| Mass / length primary structure | 535 = 193 + 342 amino acids | |
| Secondary to quaternary structure | A + B | |
| Identifier | ||
| Gene name (s) | DT | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 2.4.2.36 , glycosyl transferase | |
| Response type | Transfer of an ADP ribose residue | |
| Substrate | NAD + + EF-2 | |
| Products | NAD + EF-2 (defective) | |
The diphtheria toxin (DT) is an exotoxin of Corynebacterium diphtheriae , the causative agent of diphtheria and inhibits the protein synthesis in eukaryotes and archaea by blocking the translational during the elongation phase . The high molecular weight and heat-labile toxin is one of the lectins . The genetic information is contained in the prophage β and only when the bacterium is infected by it can it produce the toxin itself.
Mode of action
The toxin consists of two proteins, toxin A and toxin B, which are linked by disulfide bridges and binds selectively to the 80 S-ribosomes of eukaryotic cells. Its mass is about 61 kDa . There are three known functional areas ( domains ) on the toxin:
- R domain: it is a receptor binding site and enables binding to a receptor protein of the target cell
- T domain: this domain mediates the translocation of the enzyme part of the toxin into the target cell
- C domain: the enzymatic part that catalyzes ADP ribosylation (see below)
The C domain is on the A chain and the R and T domains are on the B chain.
Penetration into the cell is subject to the same mechanism as with ricin : the B chain attaches itself to a receptor on the cell surface, thereby splitting the toxin into a 21 kDa A fragment and a 40 kDa B fragment, with the A- Fragment penetrates the cell. Diphtheria toxin has this mechanism in common with many other bacterial toxins; it belongs to the group of AB toxins .
The aim of the enzymatic activity of the A-fragment is the elongation factor eEF-2, which catalyzes the translation in the protein synthesis of eukaryotes . eEF-2 contains diphthamide , an unusual amino acid residue with an unknown function that is formed from histidine . The A fragment of the toxin catalyzes the covalent modification of this diphthamide. An ADP - ribosyl residue from NAD + is transferred to a nitrogen atom in the diphthamide ring with elimination of nicotinamide . One speaks of an ADP ribosylation.
![{\ textstyle {\ ce {NAD + + eEF 2 -> [{A-chain}] ADP-ribosyl-eEF 2 + nicotinamide + H +}}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/e140666bc4576ae60ef1dcb34155323ae2f23ea7)
The diphthamide is only found in eEF-2, which explains the high specificity. The diphtheria toxin thereby inhibits the ability of the eEF-2 to translate the growing polypeptide chain. Protein synthesis stops and this is what causes the remarkable toxicity of diphtheria toxin. Just one A chain molecule is enough to kill a cell. Because of the high density of surface receptors in heart and nerve cells, these cells are the most sensitive.
The diphtheria toxin is the active ingredient in diphtheria vaccines .
Similar toxins
Other poisons that originate from pathogens also consist of two interconnected peptide chains, one of which binds to a receptor on the cell surface and thus gives the other chain access to the inside of the cell, such as cholera toxin , pertussis toxin (whooping cough toxin) and anthrax toxin . However, the toxic mechanisms of these toxins are different. Exotoxin A from Pseudomonas aeruginosa uses the same mechanism of NAD-dependent ADP-ribosylation .
literature
- Stryer Lubert: Biochemistry . Verlag Spektrum der Wissenschaft, Heidelberg 1990, ISBN 3-89330-690-0 , pp. 791-796.
Individual evidence
- ↑ Marlies Höck and Helmut Hahn: Corynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 309 .
- ↑ a b c Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 311 f .
- ↑ Jeremy M. Berg et al .: Stryer Biochemistry . 8th edition. Springer-Verlag, 2018, ISBN 978-3-662-54620-8 , pp. 1085 .