Highly specific interactions between botulinum neurotoxins and synaptic vesicle proteins
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Despite its extreme toxicity, botulinum neurotoxin is widely utilized in low doses as a treatment for several neurological disorders; higher doses cause the neuroparalytic syndrome botulism. The toxin blocks neurotransmitter release by preferentially attaching to pre-synaptic membrane receptors at neuromuscular junctions and subsequently delivering a Zn 2+-dependent protease component to presynaptic neuronal cytosol. These highly specialized enzymes exclusively hydrolyze peptide bonds within SNARE (soluble N-ethylmaleiamide sensitive factor attachment protein receptor) proteins. In this review we discuss the structural basis for botulinum toxin’s exquisite specificity for its neuronal cell-surface receptors and intracellular SNARE targets.
Keywords.SNARE botulism tetanus synaptotagmin metalloprotease endocytosis synaptic vesicle neurotransmission
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