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Unique ganglioside binding by botulinum neurotoxins C and D‐SA
Author(s) -
Kroken Abby R.,
Karalewitz Andrew P.A.,
Fu Zhuji,
Baldwin Michael R.,
Kim JungJa P.,
Barbieri Joseph T.
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08166.x
Subject(s) - ganglioside , serotype , toxin , receptor , virology , clostridium botulinum , binding site , chemistry , biology , biochemistry
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. The BoNT/C and BoNT/D serotypes include mosaic toxins that are organized as D–C and C–D toxins. One BoNT D–C mosaic toxin, BoNT/D‐South Africa (BoNT/D‐SA), was not fully neutralized by immunization with a vaccine composed of either prototype BoNT/C‐Stockholm or BoNT/D‐1873. Whereas several BoNT serotypes utilize dual receptors (gangliosides and proteins) to bind to and enter neurons, the basis for BoNT/C and BoNT/D entry into neurons is less well understood. Recent studies solved the crystal structures of the receptor‐binding domains of BoNT/C, BoNT/D, and BoNT/D‐SA. Comparative structural analysis showed that BoNT/C, BoNT/D and BoNT/D‐SA lacked components of the ganglioside‐binding pocket that exists within other BoNT serotypes. With the use of structure‐based alignments, biochemical analyses, and cell‐binding approaches, BoNT/C and BoNT/D‐SA have been shown to possess a unique ganglioside‐binding domain, the ganglioside‐binding loop. Defining how BoNTs enter host cells provides insights towards understanding the evolution and extending the potential therapeutic and immunological values of the BoNT serotypes.