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- Zhang, Sicai (author)
Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC
- Article/chapterEnglish2017
Publisher, publication year, extent ...
- 2017-11-21
- Springer Science and Business Media LLC,2017
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:su-149915
- https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-149915URI
- https://doi.org/10.1038/s41467-017-01534-zDOI
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-142969URI
Supplementary language notes
- Language:English
- Summary in:English
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Notes
- 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 and genre
- 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
Added entries (persons, corporate bodies, meetings, titles ...)
- Berntsson, Ronnie P. -A.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(Swepub:umu)robe0049 (author)
- Tepp, William H. (author)
- Tao, Liang (author)
- Johnson, Eric A. (author)
- Stenmark, PålStockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)stenm (author)
- Dong, Min (author)
- Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)
Related titles
- In:Nature Communications: Springer Science and Business Media LLC82041-1723
Internet link
- https://doi.org/10.1038/s41467-017-01534-zFulltext
- https://www.nature.com/articles/s41467-017-01534-z.pdf
- https://umu.diva-portal.org/smash/get/diva2:1166117/FULLTEXT01.pdffulltext:print
- https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-149915
- https://doi.org/10.1038/s41467-017-01534-z
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-142969
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