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

Jonathan R. Davies, Sai Man Liu, K-Ravi Acharya

Research output: Contribution to journalReview article

5 Citations (Scopus)

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.

Original languageEnglish
Article number421
Pages (from-to)1-18
Number of pages18
JournalToxins
Volume10
Issue number10
DOIs
Publication statusPublished - 20 Oct 2018

Keywords

  • SV2
  • binding domain
  • botulinum neurotoxins
  • ganglioside
  • neurones
  • synaptotagmin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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