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Clostridial Neurotoxin Light Chains: Devices for SNARE Cleavage Mediated Blockade of Neurotransmission

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Botulinum Neurotoxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 364))

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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  1. Institut für Biochemie, OE 4310, Medizinische Hochschule Hannover, 30623, Hannover, Germany

    Thomas Binz

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  1. , Institut für Toxikologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Andreas Rummel

  2. , Institut für Physiologische Chemie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Thomas Binz

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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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