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Botulinum Neurotoxins pp 21–44Cite as

Assembly and Function of the Botulinum Neurotoxin Progenitor Complex

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

Abstract

Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are high molecular weight (up to ~900 kDa) multiprotein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal (GI) tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream.

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Abbreviations

PTC:

Progenitor toxin complex

NTNHA:

Non-toxic non-hemagglutinin protein

HA:

Hemagglutinin

NAP:

Neurotoxin-associated protein

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Acknowledgments

This work was partially supported by NIH grant 5R01AI091823 to R.J.

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Authors and Affiliations

  1. Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Shenyan Gu & Rongsheng Jin

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  1. Shenyan Gu
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  2. Rongsheng Jin
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Correspondence to Rongsheng Jin .

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Editors and Affiliations

  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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Gu, S., Jin, R. (2012). Assembly and Function of the Botulinum Neurotoxin Progenitor Complex. 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_2

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