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

Neurotoxin Type A Light Chain Protein, a component of botulinum toxin, induces flaccid paralysis by disrupting neurotransmitter (acetylcholine) release from presynaptic membranes in the skeletal and autonomic nervous systems of eukaryotic hosts, often leading to respiratory or cardiac failure. The precursor of botulinum neurotoxin A2, it relies on two coreceptors—complex polysialylated gangliosides on neural tissue and specific membrane-anchored proteins in synaptic vesicles. Receptor proteins become accessible during neurotransmitter release, initiating binding with the toxin's heavy chain (HC). Following endocytic uptake and a pH-dependent structural rearrangement, the HC's N-terminus forms pores, enabling the translocation of the light chain (LC) into the cytosol. Once in the cytosol, the disulfide bond between the subunits is reduced, allowing LC to cleave its target protein, SNAP25, preventing synaptic vesicle fusion with the cytoplasmic membrane and thereby halting neurotransmitter release. The proteolytic activity of LC, specifically hydrolyzing the 197-Gln-|-Arg-198 bond in SNAP25, is crucial for its inhibitory effect on neurotransmission.