Abstract
Seven serologically distinct botulinum neurotoxins and tetanus neurotoxin which cause the diseases botulism and tetanus constitute the clostridial neurotoxin family. Like many other bacterial protein toxins they exhibit a modular structure. One domain mediates highly specific binding to target cells and endocytosis, while the second translocates the third, a catalytic domain across the endosomal membrane to the target cell cytosol. In case of Clostridial neurotoxins (CNT), the latter acts as extremely specific Zn2+-dependent metalloproteinase. The various serotypes proteolyze each one particular peptide bond in one of the three SNARE proteins, which are the core of the membrane fusion apparatus for synaptic vesicles. SNARE cleavage causes the blockade of neurotransmitter release. This chapter details the molecular basis for the highly selective substrate recognition and cleavage mechanism of CNT.
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Abbreviations
- BoNT:
-
botulinum neurotoxin
- BoNT/X:
-
serotype X of BoNT, X = A–G
- BoNT/XY:
-
subtype Y of serotype BoNT/X, Y = 1–8
- CNT:
-
clostridial neurotoxins
- HC/X:
-
heavy chain of BoNT serotype X/TeNT
- HCX:
-
50 kDa cell binding fragment of BoNT/TeNT
- HNX:
-
50 kDa translocation domain of BoNT/TeNT
- LC/X:
-
light chain, catalytic domain of BoNT serotype X/TeNT
- NSF:
-
N-ethylmaleimide-sensitive factor
- SNAP:
-
soluble NSF adapter protein
- SNAP-25:
-
synaptosomal associated protein of 25 kDa
- SNAP-23:
-
23 kDa homolog of SNAP-25
- SNARE:
-
soluble N-ethylmaleimide-sensitive factor attachment protein receptor
- syntaxin-X:
-
Isoform X of syntaxin, X = 1–19
- TI-VAMP:
-
tetanus neurotoxin insensitive VAMP
- TeNT:
-
tetanus neurotoxin
- VAMP:
-
vesicle-associated membrane protein
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Acknowledgments
I thank Andreas Rummel for critically reviewing the manuscript. This work was supported by grant BI 660/3-1from the Deutsche Forschungsgemeinschaft to T. B.
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Binz, T. (2012). Clostridial Neurotoxin Light Chains: Devices for SNARE Cleavage Mediated Blockade of Neurotransmission. In: Rummel, A., Binz, T. (eds) Botulinum Neurotoxins. Current Topics in Microbiology and Immunology, vol 364. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33570-9_7
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