title: 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.
authors: Department of Microbiology and of Molecular Genetics, Medical College of Wisconsin,Milwaukee, Wisconsin 53226-3548, USA.
authors: Andrew P-A
authors: AP
authors: Karalewitz
authors: Abby R
authors: AR
authors: Kroken
authors: Zhuji
authors: Z
authors: Fu
authors: Michael R
authors: MR
authors: Baldwin
authors: Jung-Ja P
authors: JJ
authors: Kim
authors: Joseph T
authors: JT
authors: Barbieri
mesh_terms: D055592:Biophysical Phenomena; D001905:Botulinum Toxins; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013019:South Africa
chemical_list: D005732:Gangliosides; D009498:Neurotoxins; D001905:Botulinum Toxins; C096324:botulinum toxin type C