Identification and characterization of a novel botulinum neurotoxin.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Zhang S,Masuyer G,Zhang J,Shen Y,Lundin D,Henriksson L,Miyashita SI,Martínez-Carranza M,Dong M,Stenmark P

doi

10.1038/ncomms14130

subject

Has Abstract

pub_date

2017-08-03 00:00:00

pages

14130

issn

2041-1723

pii

ncomms14130

journal_volume

8

pub_type

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