title: Clostridial neurotoxin light chains: devices for SNARE cleavage mediated blockade of neurotransmission.
abstract: Seven serologically distinct botulinum neurotoxins and tetanus neurotoxin which cause the diseases botulism and tetanus constitute the clostridial neurotoxin family. Like many other bacterial protein toxins they exhibit a modular structure. One domain mediates highly specific binding to target cells and endocytosis, while the second translocates the third, a catalytic domain across the endosomal membrane to the target cell cytosol. In case of Clostridial neurotoxins (CNT), the latter acts as extremely specific Zn(2+)-dependent metalloproteinase. The various serotypes proteolyze each one particular peptide bond in one of the three SNARE proteins, which are the core of the membrane fusion apparatus for synaptic vesicles. SNARE cleavage causes the blockade of neurotransmitter release. This chapter details the molecular basis for the highly selective substrate recognition and cleavage mechanism of CNT.
authors.affiliation: Institut für Biochemie, OE 4310, Medizinische Hochschule Hannover, 30623 Hannover, Germany. binz.thomas@mh-hannover.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Binz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D003013:Clostridium / Q000378:metabolism; D004705:Endocytosis; D004789:Enzyme Activation; D005089:Exocytosis; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D050600:SNARE Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism; D013744:Tetanus Toxin / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D014179:Neurotransmitter Uptake Inhibitors; D050600:SNARE Proteins; D013744:Tetanus Toxin; D015032:Zinc