Assembly and function of the botulinum neurotoxin progenitor complex

Curr Top Microbiol Immunol. 2013;364:21-44. doi: 10.1007/978-3-642-33570-9_2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Transport
  • Botulinum Toxins / genetics
  • Botulinum Toxins / metabolism*
  • Botulinum Toxins / toxicity
  • Clostridium botulinum / genetics
  • Clostridium botulinum / metabolism*
  • Clostridium botulinum / pathogenicity
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Hemagglutinins / metabolism
  • Host-Pathogen Interactions
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Multiprotein Complexes / metabolism*
  • Neurotoxins / genetics
  • Neurotoxins / metabolism
  • Neurotoxins / toxicity
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Sequence Analysis, Protein
  • Structure-Activity Relationship

Substances

  • Hemagglutinins
  • Multiprotein Complexes
  • Neurotoxins
  • Botulinum Toxins