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Translocation, Entry into the Cell

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Molecular Aspects of Botulinum Neurotoxin

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

Abstract

Efficient targeted delivery of bioactive proteins into the cytoplasm of living cells is a major challenge for the pharmaceutical and biotechnology industries. Botulinum toxins have evolved an elegant mechanism to achieve exactly this. They specifically target pre-synaptic active neurons with sub nanomolar affinity and deliver an enzymatically active 50 kDa protease into the cytoplasm without affecting cell viability. Recent progress in understanding the molecular details of this delivery has opened new possibilities to understand and treat the disease botulism and to harness and adapt this delivery mechanism for other uses. This review describes our current understanding of the structure, function and interactions between protein domains in botulinum toxin, which act together to translocate a large soluble protein across cell membranes. As our understanding of these processes increases so too does the potential to incorporate botulinum toxin protein domains into new engineered proteins and achieve cytoplasmic delivery of other therapeutic molecules.

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  1. Syntaxin Ltd, units 4–10, The Quadrant, Barton Lane, Abingdon, OX14 3YS, UK

    Matthew Beard

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    Keith A. Foster

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Beard, M. (2014). Translocation, Entry into the Cell. 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_7

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