Abstract
The flaccid pathology associated with intoxication by the botulinum neurotoxins (BoNTs) is the result of the association of the toxin to neuronal-specific host receptors and the cleavage of neuronal substrates, soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) proteins. Each of the seven serotypes of BoNTs (A-G) targets a specific neuronal SNARE protein(s) for cleavage. Neuronal SNARE proteins function in the binding and fusion of neurotransmitter vesicles with a host membrane, and SNARE protein cleavage by the BoNTs disrupts the fusion process leading to host paralysis. The mechanism that BoNTs utilize to bind and cleave the SNARE proteins involves recognizing an extended substrate surface to allow the BoNTs to efficiently cleave the coiled SNARE protein substrate. BoNT serotypes comprise natural variants termed subtypes, which extends the complexity and potential pathology of the BoNTs. Understanding the mechanisms of BoNT action provides tools towards the development of strategies to identify novel small-molecule inhibitors of BoNT catalysis and to extend the use of BoNTs as therapeutic agents.
Original language | English |
---|---|
Title of host publication | Molecular Aspects of Botulinum Neurotoxin |
Publisher | Springer New York |
Pages | 171-189 |
Number of pages | 19 |
ISBN (Electronic) | 9781461494546 |
ISBN (Print) | 9781461494539 |
DOIs | |
Publication status | Published - 1 Jan 2014 |
Keywords
- "Pocket" model
- Belt region
- Botulinum neurotoxin
- Exosites
- Scissile bond
- SNARE proteins
- Synaptobrevin
- Synaptosomal-associated protein of 25 kDa (SNAP- 25)
- Syntaxin
- t-SNARE
- v-SNARE
- Vesicle associated membrane protein (VAMP)
- Zincmetalloprotease
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
- General Medicine