tetanus neurotoxin (TeNT), toxins acting inside the axon terminal.<unk>  exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to nerves that use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis. As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin that triggers it to push across the vesicle membrane and into the cell cytoplasm.<unk> s recognize distinct classes of receptors simultaneously (gangliosides, synaptotagmin and SV2). Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles cannot bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to paralysis. The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide. The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to presynaptic nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies. The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family, which is responsible for fusion. The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell. The seven toxin serotypes (A–G) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences. While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members. The A, B, and E serotypes cause human<unk> ulism, with the activities of types A and B enduring longest in vivo (from several weeks to months). Existing toxin types can recombine to create "hybrid" (mosaic, chimeric) types. Examples include<unk> /CD,<unk> /DC, and<unk> /FA, with the first letter indicating the light chain type and the latter indicating the heavy chain type.<unk> /FA received considerable attention under the name "BoNT/H", as it was mistakenly thought it could not be neutralized by any existing antitoxin.<unk> s are closely related to tetanus toxin; the two are collectively known as Clostridium neurotoxins and the light chain is classified by MEROPS as family M27. Nonclassical types include<unk> /X (), which is toxic in mice and possibly in humans; a<unk> /J () found in cow Enterococcus; and a<unk> /Wo () found in the rice-colonizing Weissella oryzae.
Botulinum toxin
Bungarotoxin
Brevetoxin
Latrotoxin
Kurtoxin
Charybdotoxin
Tetrodotoxin
Α-Bungarotoxin