title: Unique ganglioside binding by 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. 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Abby R
authors.initials: AR
authors.lastname: Kroken
authors.forename: Andrew P-A
authors.initials: AP
authors.lastname: Karalewitz
authors.forename: Zhuji
authors.initials: Z
authors.lastname: Fu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Baldwin
authors.forename: Jung-Ja P
authors.initials: JJ
authors.lastname: Kim
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Barbieri
mesh_terms: D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009498:Neurotoxins / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D005732:Gangliosides; D009498:Neurotoxins; D001905:Botulinum Toxins; C096324:botulinum toxin type C