Year: 2018
Type: review
Abstract: 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.
Source: Annual Review of Biochemistry
Authors: Min Dong, Geoffrey Masuyer, Pål Stenmark
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Cancerfonden, Vetenskapsrådet, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, Harvard Digestive Diseases Center, Harvard University, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G332990701, Structural and biophysical studies of the Botulinum neurotoxins, deadly toxins that also can heal., Molecular mechanism for retrograde transport of tetanus neurotoxin, G5857948765, Molecular basis of action and pathogenesis of Clostridium difficile toxin B, Intellectual and Developmental Disablities Research Center, Integrated Epithelial and Muscosal Biology, Biology and Engineering of Botulinum Neurotoxins.
OpenAlex ID: W2903612881