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Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC

Author

Listed:
  • Sicai Zhang

    (Boston Children’s Hospital, Harvard Medical School
    Harvard Medical School)

  • Ronnie P.-A. Berntsson

    (Stockholm University
    Umeå University)

  • William H. Tepp

    (University of Wisconsin)

  • Liang Tao

    (Boston Children’s Hospital, Harvard Medical School
    Harvard Medical School)

  • Eric A. Johnson

    (University of Wisconsin)

  • Pål Stenmark

    (Stockholm University)

  • Min Dong

    (Boston Children’s Hospital, Harvard Medical School
    Harvard Medical School)

Abstract

Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A–G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides. Using liposome flotation assays, we demonstrate that an extended loop in BoNT/DC directly interacts with lipid membranes, and the co-occurring sialic acid binding and loop–membrane interactions mediate the recognition of gangliosides in membranes by BoNT/DC. These findings reveal a unique mechanism for cell membrane recognition and demonstrate that BoNT/DC can use a broad range of sialic acid-containing moieties as co-receptors.

Suggested Citation

  • Sicai Zhang & Ronnie P.-A. Berntsson & William H. Tepp & Liang Tao & Eric A. Johnson & Pål Stenmark & Min Dong, 2017. "Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01534-z
    DOI: 10.1038/s41467-017-01534-z
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