期刊
BIOCHEMISTRY
卷 49, 期 37, 页码 8117-8126出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi100865f
关键词
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资金
- National Institutes of Health Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research Program
- Great Lakes Regional Center of Excellence [1-U54-AI-057153]
- National Institute of Neurological Disorders and Stroke [NS061763]
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.
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