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Identification and characterization of a novel botulinum neurotoxin
Harvard Med Sch, USA.
Stockholm University.ORCID iD: 0000-0002-9527-2310
Harvard Med Sch, USA.
Harvard Med Sch, USA.ORCID iD: 0000-0003-4117-0279
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 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
Nature Publishing Group, 2017. Vol. 8, article id 14130
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Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
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URN: urn:nbn:se:lnu:diva-73794DOI: 10.1038/ncomms14130ISI: 000406846300001PubMedID: 28770820OAI: oai:DiVA.org:lnu-73794DiVA, id: diva2:1203581
Available from: 2018-05-03 Created: 2018-05-03 Last updated: 2018-05-03Bibliographically approved

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Lundin, Daniel

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