Structural analysis of botulinum neurotoxins type B and E by Cryo-EM
Košenina, Sara ; Martínez-Carranza, Markel ; Davies, Jonathan R. ; Masuyer, Geoffrey and Stenmark, Pål LU
(2022)
In Toxins
14(1).
- 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... (More)
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.
(Less)
- author
- Košenina, Sara
; Martínez-Carranza, Markel
; Davies, Jonathan R.
; Masuyer, Geoffrey
and Stenmark, Pål
LU
- organization
- publishing date
- 2022-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- BoNT/B, BoNT/E, Botulinum neurotoxin, Botulism, Clostridium botulinum, Cryo-EM
- in
- Toxins
- volume
- 14
- issue
- 1
- article number
- 14
- publisher
- MDPI AG
- external identifiers
-
- pmid:35050991
- scopus:85121826033
- ISSN
- 2072-6651
- DOI
- 10.3390/toxins14010014
- language
- English
- LU publication?
- yes
- id
- 0e787c85-ecc6-417a-884b-6bc38f378208
- date added to LUP
- 2022-02-28 15:32:52
- date last changed
- 2024-06-22 15:37:29
@article{0e787c85-ecc6-417a-884b-6bc38f378208,
abstract = {{<p>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.</p>}},
author = {{Košenina, Sara and Martínez-Carranza, Markel and Davies, Jonathan R. and Masuyer, Geoffrey and Stenmark, Pål}},
issn = {{2072-6651}},
keywords = {{BoNT/B; BoNT/E; Botulinum neurotoxin; Botulism; Clostridium botulinum; Cryo-EM}},
language = {{eng}},
number = {{1}},
publisher = {{MDPI AG}},
series = {{Toxins}},
title = {{Structural analysis of botulinum neurotoxins type B and E by Cryo-EM}},
url = {{http://dx.doi.org/10.3390/toxins14010014}},
doi = {{10.3390/toxins14010014}},
volume = {{14}},
year = {{2022}},
}