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Toxins 2018, 10(10), 421; https://doi.org/10.3390/toxins10100421

Variations in the Botulinum Neurotoxin Binding Domain and the Potential for Novel Therapeutics

1
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
2
Ipsen Bioinnovation Limited, Abingdon OX14 4RY, UK
*
Author to whom correspondence should be addressed.
Received: 21 September 2018 / Revised: 11 October 2018 / Accepted: 18 October 2018 / Published: 20 October 2018
(This article belongs to the Special Issue Bacterial Toxins: Structure–Function Relationship)
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Abstract

Botulinum neurotoxins (BoNTs) are categorised into immunologically distinct serotypes BoNT/A to /G). Each serotype can also be further divided into subtypes based on differences in amino acid sequence. BoNTs are ~150 kDa proteins comprised of three major functional domains: an N-terminal zinc metalloprotease light chain (LC), a translocation domain (HN), and a binding domain (HC). The HC is responsible for targeting the BoNT to the neuronal cell membrane, and each serotype has evolved to bind via different mechanisms to different target receptors. Most structural characterisations to date have focussed on the first identified subtype within each serotype (e.g., BoNT/A1). Subtype differences within BoNT serotypes can affect intoxication, displaying different botulism symptoms in vivo, and less emphasis has been placed on investigating these variants. This review outlines the receptors for each BoNT serotype and describes the basis for the highly specific targeting of neuronal cell membranes. Understanding receptor binding is of vital importance, not only for the generation of novel therapeutics but also for understanding how best to protect from intoxication. View Full-Text
Keywords: botulinum neurotoxins; binding domain; ganglioside; SV2; synaptotagmin; neurones botulinum neurotoxins; binding domain; ganglioside; SV2; synaptotagmin; neurones
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Davies, J.R.; Liu, S.M.; Acharya, K.R. Variations in the Botulinum Neurotoxin Binding Domain and the Potential for Novel Therapeutics. Toxins 2018, 10, 421.

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