Structure and function of tetanus and botulinum neurotoxins
10.1017/s0033583500003292
Crossref journal-article
Cambridge University Press (CUP)
Quarterly Reviews of Biophysics (56)
Abstract

Tetanus and botulinum neurotoxins are produced byClostridiaand cause the neuroparalytic syndromes of tetanus and botulism. Tetanus neurotoxin acts mainly at the CNS synapse, while the seven botulinum neurotoxins act peripherally. Clostridial neurotoxins share a similar mechanism of cell intoxication: they block the release of neurotransmitters. They are composed of two disulfide-linked polypeptide chains. The larger subunit is responsible for neurospecific binding and cell penetration. Reduction releases the smaller chain in the neuronal cytosol, where it displays its zinc-endopeptidase activity specific for protein components of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxins B, D, F and G recognize specifically VAMP/synaptobrevin. This integral protein of the synaptic vesicle membrane is cleaved at single peptide bonds, which differ for each neurotoxin. Botulinum A, and E neurotoxins recognize and cleave specifically SNAP-25, a protein of the presynaptic membrane, at two different sites within the carboxyl-terminus. Botulinum neurotoxin type C cleaves syntaxin, another protein of the nerve plasmalemma. These results indicate that VAMP, SNAP-25 a n d syntaxin play a central role in neuroexocytosis. These three proteins are conserved from yeast to humans and are essential in a variety of docking and fusion events in every cell. Tetanus and botulinum neurotoxins form a new group of zinc-endopeptidases with characteristic sequence, mode of zinc coordination, mechanism of activation and target recognition. They will be of great value in the unravelling of the mechanisms of exocytosis and endocytosis, as they are in the clinical treatment of dystonias.

Bibliography

Montecucco, C., & Schiavo, G. (1995). Structure and function of tetanus and botulinum neurotoxins. Quarterly Reviews of Biophysics, 28(4), 423–472.

Authors 2
  1. Cesare Montecucco (first)
  2. Giampietro Schiavo (additional)
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Dates
Type When
Created 16 years, 5 months ago (March 17, 2009, 11:33 a.m.)
Deposited 6 months, 3 weeks ago (Feb. 8, 2025, 8:19 a.m.)
Indexed 6 days, 21 hours ago (Aug. 23, 2025, 9:36 p.m.)
Issued 29 years, 9 months ago (Nov. 1, 1995)
Published 29 years, 9 months ago (Nov. 1, 1995)
Published Online 16 years, 5 months ago (March 17, 2009)
Published Print 29 years, 9 months ago (Nov. 1, 1995)
Funders 0

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@article{Montecucco_1995, title={Structure and function of tetanus and botulinum neurotoxins}, volume={28}, ISSN={1469-8994}, url={http://dx.doi.org/10.1017/s0033583500003292}, DOI={10.1017/s0033583500003292}, number={4}, journal={Quarterly Reviews of Biophysics}, publisher={Cambridge University Press (CUP)}, author={Montecucco, Cesare and Schiavo, Giampietro}, year={1995}, month=nov, pages={423–472} }