Clostridial Neurotoxins

Synaptotagmins I and II Act as Nerve Cell Receptors for Botulinum Neurotoxin G

“…This agrees with the notion that none of the remaining six CNTs binds to Syt-I or Syt-II and the observation that BoNT/B and -G are incapable of competing binding of BoNT/A and E to synaptosomal membranes. 2 These data add further support to the premise that all other CNTs associate with different protein receptors to become endocytosed. Interestingly, TeNT, which is sorted into the retrograde axonal transport route upon endocytosis, was demonstrated to bind simultaneously to two separate carbohydrate structures (16,26), one of which could be part of the recently discovered glycosylated 15-kDa protein receptor (27).…”

“…Their light chains (LCs) act as zinc-dependent endopeptidases and specifically hydrolyze certain proteins of the vesicular fusion machinery, whereupon the Ca 2ϩ -triggered fusion of synaptic vesicles with the presynaptic membrane is disrupted (reviewed in Refs. [1][2][3]. The heavy chains (HCs) are tethered to the LCs via a single disulfide bond and encompass the three remaining domains.…”

Botulinum toxin A does not alter capsaicin-induced pain perception in human skin

“…Thus, BoNT/A is an effective peripheral muscle relaxant for the treatment of symptoms in which a pathologically increased muscle tone is responsible, such as dystonic and spastic movement disorders [3][4][5]. The mechanism of this action is due to proteolytic cleavage of SNAP-25, a constituent of the protein complex that fuses the membranes of acetylcholine containing vesicles and presynaptic nerve endings [6,7]. BoNT/A is effective not only in nerve endings of motor neurons but also in those of other cholinergic neurons, e.g.…”

The HC Fragment of Tetanus Toxin forms Stable, Concentration-dependent Dimers via an Intermolecular Disulphide Bond

“…1 CNTs are proteins of approximately 150 kDa consisting of a 50 kDa light (L) chain, containing an active site for proteolysis, which is disulphidebonded to a 100 kDa heavy (H) chain. The H chain is composed of a translocation (H N ) and a binding (H C ) domain, each of approximately 50 kDa.…”