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Structural basis fo...
Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC
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Zhang, Sicai (author)
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- Berntsson, Ronnie P. -A. (author)
- Umeå universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Umeå University, Sweden,Institutionen för medicinsk kemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden
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Tepp, William H. (author)
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Tao, Liang (author)
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Johnson, Eric A. (author)
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- Stenmark, Pål (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Dong, Min (author)
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(creator_code:org_t)
- 2017-11-21
- 2017
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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