期刊
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 88
卷 88, 期 -, 页码 811-837出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-biochem-013118-111654
关键词
botulinum neurotoxin; tetanus neurotoxin; bacterial toxin; toxin; clostridium; protein engineering
资金
- NIAID NIH HHS [R01 AI132387] Funding Source: Medline
- NICHD NIH HHS [P30 HD018655] Funding Source: Medline
- NIDDK NIH HHS [P30 DK034854] Funding Source: Medline
- NINDS NIH HHS [R21 NS106159, R01 NS080833] Funding Source: Medline
Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering.
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