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Identification and characterization of a novel botulinum neurotoxin

Author

Listed:
  • Sicai Zhang

    (Boston Children’s Hospital, Harvard Medical School)

  • Geoffrey Masuyer

    (Stockholm University)

  • Jie Zhang

    (Boston Children’s Hospital, Harvard Medical School)

  • Yi Shen

    (Boston Children’s Hospital, Harvard Medical School)

  • Daniel Lundin

    (Stockholm University)

  • Linda Henriksson

    (Stockholm University)

  • Shin-Ichiro Miyashita

    (Boston Children’s Hospital, Harvard Medical School)

  • Markel Martínez-Carranza

    (Stockholm University)

  • Min Dong

    (Boston Children’s Hospital, Harvard Medical School)

  • Pål Stenmark

    (Stockholm University)

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.

Suggested Citation

  • Sicai Zhang & Geoffrey Masuyer & Jie Zhang & Yi Shen & Daniel Lundin & Linda Henriksson & Shin-Ichiro Miyashita & Markel Martínez-Carranza & Min Dong & Pål Stenmark, 2017. "Identification and characterization of a novel botulinum neurotoxin," Nature Communications, Nature, vol. 8(1), pages 1-10, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14130
    DOI: 10.1038/ncomms14130
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    Cited by:

    1. Oneda Leka & Yufan Wu & Giulia Zanetti & Sven Furler & Thomas Reinberg & Joana Marinho & Jonas V. Schaefer & Andreas Plückthun & Xiaodan Li & Marco Pirazzini & Richard A. Kammerer, 2023. "A DARPin promotes faster onset of botulinum neurotoxin A1 action," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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