Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA

Journal Article · Wed Sep 22 00:00:00 EDT 2010 · Biochemistry-US

DOI:https://doi.org/10.1021/bi100865f· OSTI ID:1002722

Karalewitz, Andrew P.-A.; Kroken, Abby R; Fu, Zhuji; Baldwin, Michael R; Kim, Jung-Ja P; Barbieri, Joseph T ^[1]

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1. MCW

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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1002722
• Journal Information: Biochemistry-US, Vol. 49, Issue (37) ; 09, 2010; ISSN 0006-2960
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
AFRICA
CRYSTAL STRUCTURE
GANGLIOSIDES
IMMUNE SERUMS
NERVE CELLS
PROTEINS
TOXINS