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Protease Activity of the Botulinum Neurotoxins

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Molecular Aspects of Botulinum Neurotoxin

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 4))

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-ethylmaleimide-sensitive 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.

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Acknowledgments

JTB acknowledges membership in the GLRCE and support by 1-U54-AI-057153 from Region V Great Lakes Regional Center of Excellence, the National Institute of Allergy and Infectious Diseases (NIAID), and National Institutes of Health Regional Center of Excellence for Bio-defense and Emerging Infectious Diseases Research Program and NIH-AI-030162. Sheng Chen is funded from the Research Grants Council (RGC)/PolyU Competitive Research Grants: G-U662, A-PK05, and G-YJ15.

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  1. The Hong Kong Polytechnic University, Hung Hom, Hong Kong

    Sheng Chen

  2. Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, USA

    Joseph T. Barbieri

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  1. Sheng Chen
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Correspondence to Sheng Chen .

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  1. Units 4-10, Syntaxin Ltd., Abingdon, Oxfordshire, United Kingdom

    Keith A. Foster

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Chen, S., Barbieri, J. (2014). Protease Activity of the Botulinum Neurotoxins. In: Foster, K. (eds) Molecular Aspects of Botulinum Neurotoxin. Current Topics in Neurotoxicity, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9454-6_8

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