Botulinum Neurotoxin Serotype D (BoNT/D)

Botulinum neurotoxin serotype D (BoNT/D) is one of the seven immunologically distinct serotypes of botulinum neurotoxins produced by *Clostridium botulinum* and related species. BoNT/D is a potent neurotoxin primarily associated with outbreaks of botulism in cattle and horses. It functions as a zinc-dependent endopeptidase that cleaves VAMP1 and VAMP2, SNARE proteins essential for acetylcholine release, resulting in flaccid paralysis.

BoNT/D binds specifically to presynaptic nerve terminals at neuromuscular junctions using dual receptors: gangliosides and synaptic vesicle protein SV2. After receptor-mediated endocytosis into neurons, acidification triggers translocation of the light chain into the cytoplasm. The light chain cleaves SNARE proteins—specifically VAMP1 and VAMP2/synaptobrevin—inhibiting acetylcholine release from presynaptic terminals. This results in flaccid paralysis characteristic of botulism.