Tetanospasmin
| Tetanospasmin | ||
|---|---|---|
| Mass / length primary structure | 1314 = 456 + 858 amino acids | |
| Cofactor | Zn 2+ | |
| Precursor | (1315 aa) | |
| Identifier | ||
| Gene name (s) | tetX | |
| External IDs |
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| Transporter classification | ||
| TCDB | 1.C.8.1.2 | |
| designation | Botulinum / tetanus toxin family | |
| Enzyme classification | ||
| EC, category | 3.4.24.68 , metalloprotease | |
| MEROPS | M27.001 | |
| Response type | hydrolysis | |
| Substrate | 76-Gln - + - Phe-77 in Synaptobrevin 2 | |
| Products | Fission products | |
| Occurrence | ||
| Homology family | Botulinum toxin | |
| Parent taxon | Clostridium | |
| safety instructions | |||||||
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| CAS number |
676570-37-9 |
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The tetanus toxin or Tetanospasmin is the most important that of Clostridium tetani formed exotoxins . It is a 150 kDa large protein and is active both by the bacteria secreted as well as lysis released by bacteria. It has a direct neurotoxic effect through proteolysis of the SNARE proteins.
construction
The toxin consists of two subunits and is formed intracellularly from a proto-polypeptide during the logarithmic growth phase. After autolysis, the prototoxin is converted into its active form by proteases . The heavy protein chain (100 kDa with two domains ) is responsible for binding the toxin to gangliosides of nerve cells (i.e. binding to the membrane and translocation through the membrane), while the light chain (50 kDa) mediates neurotoxicity. The light and heavy chain as well as the two domains of the heavy protein chain are each linked by a disulfide bridge.
The C-terminus of the heavy chain binds to receptors necessary for endocytosis. The N-terminus mediates the intra- axonal transport and, in the central interneuron, also the translocation of the toxin into the cytosol of the neuron. The light chain is necessary for the toxin-specific properties.
The genes for the toxin are highly conserved and its regulatory gene is on a plasmid .
effect
The toxin presynaptically inhibits the inhibitory synapses on the spinal motor neurons and the release of the neurotransmitters glycine and GABA . Clinically this shows up in a spastic paralysis .
Similar toxins
It is the second most powerful bacterial toxin after botulinum toxin. It is estimated that the minimum lethal dose for humans is less than 2.5 ng per kg of body weight. Like this, it cleaves the vesicle membrane protein synaptobrevin . In addition, tetanospasmin has a similar effect to the plant poison strychnine , which also prevents the effects of glycine.
Others
Tetanospasmin is detected in animal experiments if there is urgent suspicion. Mice typically show seal pose. Even 0.1 ng / kg body weight tetanospasmin kill a mouse, 0.3 ng / kg KW a guinea pig . While mice, guinea pigs, monkeys, sheep and goats are very sensitive to the toxin, cats, dogs, birds and cold blooded animals are more resistant.
Tetanospasmin can be inactivated by formalin , thus obtaining the toxoid vaccine , which is used as an effective component of a tetanus vaccine for active tetanus vaccination .
The German toxicologist Ernst Habermann did pioneering work in the elucidation of the structure and mode of action of tetanospasmin.
Individual evidence
- ↑ a b c Datasheet tetanus toxin, from Clostridium tetani at Sigma-Aldrich , accessed on July 29, 2017 ( PDF ).
- ↑ R. Pellizzari et al .: Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses . In: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences . tape 354 , no. 1381 , February 28, 1999, p. 259-268 , doi : 10.1098 / rstb.1999.0377 , PMID 10212474 , PMC 1692495 (free full text).
- ↑ Thomas Binz et al .: Clostridial neurotoxins: mechanism of SNARE cleavage and outlook on potential substrate specificity reengineering . In: Toxins . tape 2 , no. 4 , April 2010, p. 665-682 , doi : 10.3390 / toxins2040665 , PMID 22069605 , PMC 3153214 (free full text).
- ↑ a b c d Stanley A. Plotkin et al .: Plotkin's Vaccines . 7th edition. Elsevier, Philadelphia 2017, ISBN 978-0-323-35761-6 , pp. 1052 ff . ( elsevier.com ).
- ↑ BENEFIT DOCUMENTATION OF STANDARD VACCINES: TETANUS. Arznei-Telegram , February 19, 2016, pp. 17–20 , accessed on December 10, 2019 .