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 language | English |
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Article number | 14 |
Journal | Toxins |
Volume | 14 |
Issue number | 1 |
DOIs | |
Publication status | Published - 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.
Funding
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. 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 Ume? University.
Keywords
- BoNT/B
- BoNT/E
- Botulinum neurotoxin
- Botulism
- Clostridium botulinum
- Cryo-EM
ASJC Scopus subject areas
- Toxicology
- Health, Toxicology and Mutagenesis