Structural analysis of botulinum neurotoxins type B and E by Cryo-EM

Sara Košenina, Markel Martínez-Carranza, Jonathan R. Davies, Geoffrey Masuyer, Pål Stenmark

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)

Abstract

Botulinum neurotoxins (BoNTs) are the causative agents of a potentially lethal paralytic disease targeting cholinergic nerve terminals. Multiple BoNT serotypes exist, with types A, B and E being the main cause of human botulism. Their extreme toxicity has been exploited for cosmetic and therapeutic uses to treat a wide range of neuromuscular disorders. Although naturally occurring BoNT types share a common end effect, their activity varies significantly based on the neuronal cell-surface receptors and intracellular SNARE substrates they target. These properties are the result of structural variations that have traditionally been studied using biophysical methods such as X-ray crystallography. Here, we determined the first structures of botulinum neurotoxins using single-particle cryogenic electron microscopy. The maps obtained at 3.6 and 3.7 Å for BoNT/B and /E, respectively, highlight the subtle structural dynamism between domains, and of the binding domain in particular. This study demonstrates how the recent advances made in the field of single-particle electron microscopy can be applied to bacterial toxins of clinical relevance and the botulinum neurotoxin family in particular.

Original languageEnglish
Article number14
JournalToxins
Volume14
Issue number1
DOIs
Publication statusPublished - 23 Dec 2021

Keywords

  • BoNT/B
  • BoNT/E
  • Botulinum neurotoxin
  • Botulism
  • Clostridium botulinum
  • Cryo-EM

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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