Tetanus toxin mode of action

Tetanus toxin is synthesised as a 150kDa polypeptide chain (100kDa heavy chain (HC) required for cell entry and a 50kDa light chain (LC) which causes disease. The C-terminal domain of the HC binds to gangliosides, whilst the N-terminal domain of the HC allows the LC to cross into the cell cytoplasm. Once in the cytoplasm the LC interrupts release of neurotransmitters. LC is a zinc metalloprotease which cleaves synaptobrevin 2, a SNARE protein involved in the fusion of neurotransmitter vesicles with the neuronal membrane. By cleaving synaptobrevin 2 vesicles containing GABA and glycine are not allowed to dock and hence no neurotransmitter can be released.