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Identification and characterization of a novel botulinum neurotoxin
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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Number of Authors: 10
2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, 14130Article in journal (Refereed) Published
Abstract [en]

Botulinum neurotoxins are known to have seven serotypes (BoNT/A-G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X is the only toxin that also cleaves non-canonical substrates VAMP4, VAMP5 and Ykt6. To validate its activity, a small amount of full-length BoNT/X was assembled by linking two non-toxic fragments using a transpeptidase (sortase). Assembled BoNT/X cleaves VAMP2 and VAMP4 in cultured neurons and causes flaccid paralysis in mice. Thus, BoNT/X is a novel BoNT with a unique substrate profile. Its discovery posts a challenge to develop effective countermeasures, provides a novel tool for studying intracellular membrane trafficking, and presents a new potential therapeutic toxin for modulating secretions in cells.

Place, publisher, year, edition, pages
2017. Vol. 8, 14130
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-145842DOI: 10.1038/ncomms14130ISI: 000406846300001OAI: oai:DiVA.org:su-145842DiVA: diva2:1135885
Available from: 2017-08-24 Created: 2017-08-24 Last updated: 2017-08-24Bibliographically approved

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Masuyer, GeoffreyLundin, DanielHenriksson, LindaMartinez-Carranza, MarkelStenmark, Pål
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