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

3 Citations (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

Bibliographical note

Funding Information:
Funding: This work was supported by grants from the Novo Nordisk Foundation (NNF20OC0064789), the Swedish Research Council (2018-03406) and the Swedish Cancer Society (20 1287 PjF) to P.S. G.M. was supported by a Research Fellowship from Applied Molecular Transport Inc. (San Francisco, CA, USA) at the University of Bath (UK). The data was collected at the Cryo-EM Swedish National Facility funded by the Knut and Alice Wallenberg, Family Erling Persson and Kempe Foundations, SciLifeLab, Stockholm University and Umeå University.

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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