Highly specific interactions between botulinum neurotoxins and synaptic vesicle proteins.
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 Zn2+-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.
Brunger
A T
AT
Howard Hughes Medical Institute, Stanford, CA, USA. brunger@stanford.edu
Jin
R
R
Breidenbach
M A
MA
D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D011485:Protein Binding; D050600:SNARE Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D018377:Neurotransmitter Agents; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins