The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain
Abstract
<jats:title>Abstract</jats:title><jats:p>The genome of <jats:italic>Weissella oryzae</jats:italic> SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the <jats:italic>Clostridium</jats:italic> genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified <jats:italic>Weissella</jats:italic> metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.</jats:p>
Journal
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- Scientific Reports
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Scientific Reports 6 (1), 2016-07-22
Springer Science and Business Media LLC
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Keywords
Details 詳細情報について
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- CRID
- 1362262946360062080
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- ISSN
- 20452322
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- Data Source
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- Crossref