Botulinum neurotoxin type E heavy chain SV2 receptor-binding domain (BoNT/E-HCC)

Botulinum neurotoxin type E (BoNT/E) is a potent protein toxin produced by Clostridium botulinum that causes botulism, a severe paralytic illness characterized by rapid onset and high potency. The heavy chain SV2 receptor-binding domain (Hcc) is the C-terminal portion of the toxin responsible for high-affinity binding to the luminal domain of Synaptic Vesicle Protein 2 (SV2) isoforms A, B, and C on the presynaptic membrane of neurons (UniProt P30996; Dong et al., Science 2006). This binding, often facilitated by an initial interaction with gangliosides, triggers the endocytosis of the toxin into the neuron (Mahrhold et al., FEBS Lett 2006). Once internalized, the toxin's light chain is translocated into the cytosol, where it cleaves SNAP-25, preventing the release of acetylcholine and leading to flaccid paralysis (UniProt P30996). Because this domain is essential for neuronal entry, it is a primary target for the development of neutralizing antibodies and antitoxins (FDA, BAT Label). Therapeutic intervention typically involves the administration of equine-derived antitoxins, such as Botulism Antitoxin Heptavalent (BAT), which bind to the toxin in the bloodstream and prevent its interaction with neuronal receptors (CDC, Botulism Treatment).

Other names

BoNT/E-HCBotulinum neurotoxin type E C-terminal domainBoNT/E receptor-binding domainBotulinum neurotoxin type E Hcc domainClostridium botulinum neurotoxin type E heavy chain

Neutralization of the toxin by preventing its binding to the SV2 receptor on the presynaptic membrane of motor neurons, thereby blocking toxin internalization and subsequent paralysis.