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Identification of a unique ganglioside binding loop within botulinum neurotoxins C and D-SA .

ABSTRACT: The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, which stimulated this study. Here the crystal structures of the receptor binding domains of BoNT/C, BoNT/D, and BoNT/D-SA are presented. Biochemical and cell binding studies show that BoNT/C and BoNT/D-SA possess unique mechanisms for ganglioside binding. These studies provide new information about how the BoNTs can enter host cells as well as a basis for understanding the immunological diversity of these neurotoxins.

SUBMITTER: Karalewitz AP

PROVIDER: S-EPMC2939319 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Identification of a unique ganglioside binding loop within botulinum neurotoxins C and D-SA .

Karalewitz Andrew P-A AP Kroken Abby R AR Fu Zhuji Z Baldwin Michael R MR Kim Jung-Ja P JJ Barbieri Joseph T JT

Biochemistry 20100901 37

The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, w ...[more]

PMID: 20731382

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Unique ganglioside binding by botulinum neurotoxins C and D-SA.

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