Identification and characterization of a novel botulinum neurotoxin

Sicai Zhang, Geoffrey Masuyer, Jie Zhang, Yi Shen, Linda Henriksson, Shin Ichiro Miyashita, Marke Martínez-Carranza, Min Dong, Paa Stenmark

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

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.& copy.

Original languageEnglish
Article number14130
Number of pages10
JournalNature Communications
Volume8
Early online date3 Aug 2017
DOIs
Publication statusPublished - 3 Aug 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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