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The Botulinum Neurotoxin Complex and the Role of Ancillary Proteins

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Molecular Aspects of Botulinum Neurotoxin

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

Abstract

All seven known serotypes of botulinum neurotoxin (BoNT) are produced in the form of a complex with a group of neurotoxin-associated proteins (NAPs). The BoNT complex is encoded by a gene cluster regulated by its own transcription factor, and the proteins coded by polycistronic messenger ribonucleic acid (mRNA) self-assemble into complexes of 300–900 kDa. Types A, B, C, D, and G complexes contain hemagglutinin (HA), whereas types E and F complexes do not contain HA. Sequence homology among respective BoNTs and NAPs range from 55.3 to 98.5 %, and all the proteins in the BoNT complex belong to a stable class of protein with high longevity inside mammalian cells. A new 250-kDa protein (P-250) with high immunogenicity has been identified in the BoNT/A complex which is not part of the neurotoxin gene cluster. The 33-kDa hemagglutinin (HA-33) is the most abundant NAP. The HA-33 is protease resistant and is highly immunogenic. HA-33 appears to play an important role in the translocation of the neurotoxin across the gut wall, enhancing the endopeptidase activity of BoNT and protection of BoNT against proteases. The role of other NAPs is not as clear, and their role in the biology of the bacteria is not understood at all. BoNT complexes are used as therapeutic product, although a therapeutic product without NAPs appears to retain the properties of the complex-based products. NAPs in therapeutic products may have other subtle long-term effects which need to be investigated.

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Acknowledgments

This work was in part supported by grants and contracts from NIH and the Defense Threat Reduction Agency (DTRA).

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Authors and Affiliations

  1. Botulinum Research Center, Institute of Advanced Sciences, 166 Chase Road, Dartmouth, MA, 02747, USA

    Bal Ram Singh

  2. Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, Dartmouth, MA, 02747, USA

    Tzuu-Wang Chang, Roshan Kukreja & Shuowei Cai

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  1. Bal Ram Singh
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  2. Tzuu-Wang Chang
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  3. Roshan Kukreja
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  4. Shuowei Cai
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Correspondence to Bal Ram Singh .

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

    Keith A. Foster

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Singh, B., Chang, TW., Kukreja, R., Cai, S. (2014). The Botulinum Neurotoxin Complex and the Role of Ancillary Proteins. 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_4

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