Neurotoxin Type B Light Chain Protein, Botulinum (P. pastoris, His)

Neurotoxin Type B Light Chain Protein, a pivotal component of botulinum toxin, induces flaccid paralysis by impeding neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals in the eukaryotic host's skeletal and autonomic nervous system, often leading to heart or respiratory failure. As the precursor of botulinum neurotoxin B, it engages two coreceptors: complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins in synaptic vesicles. Receptor proteins are exposed on the host presynaptic cell membrane during neurotransmitter release, where the toxin heavy chain binds to them. Following synaptic vesicle recycling, the toxin is taken up via the endocytic pathway. A drop in endosomal pH triggers a structural rearrangement allowing the N-terminus of the heavy chain to form pores, facilitating the translocation of the light chain into the cytosol. Once in the cytosol, the disulfide bond between the two subunits is reduced, enabling the light chain to cleave its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release. The toxin binds to host peripheral neuronal presynaptic membranes via synaptotagmins 1 and 2, with gangliosides enhancing binding and uptake. BoNT/B acts as a 'coincidence detector,' requiring simultaneous binding to coreceptor GT1b and low pH to transform into a membrane-bound, oligomeric channel. Whole toxin exhibits protease activity after reduction, releasing the light chain, which, once translocated into the host cytosol, acts as a zinc endopeptidase inhibiting neurotransmitter release by cleaving the '76-Gln-|-Phe-77' bond of synaptobrevin-2/VAMP2.