Identification of a unique ganglioside binding loop within botulinum neurotoxins C and D-SA .
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.
Karalewitz
Andrew P-A
AP
Department of Microbiology and of Molecular Genetics, Medical College of Wisconsin,Milwaukee, Wisconsin 53226-3548, USA.
Kroken
Abby R
AR
Fu
Zhuji
Z
Baldwin
Michael R
MR
Kim
Jung-Ja P
JJ
Barbieri
Joseph T
JT
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
D005732:Gangliosides; D009498:Neurotoxins; D001905:Botulinum Toxins; C096324:botulinum toxin type C