Botulinum neurotoxin type B heavy chain C-terminal domain (BoNT/B-Hc)

The Botulinum neurotoxin type B heavy chain C-terminal domain (BoNT/B-Hc) is the specialized region of the neurotoxin responsible for highly specific binding to the presynaptic membranes of motor neurons. It functions via a dual-receptor mechanism, interacting simultaneously with complex polysialated gangliosides (such as GT1b) and the luminal domain of synaptic vesicle proteins Synaptotagmin I and II. This binding is the critical first step in the toxin's entry into the neuron, where the light chain eventually cleaves VAMP/synaptobrevin to inhibit neurotransmitter release. In a therapeutic context, the Hc domain is the primary target for neutralizing antibodies found in botulism antitoxins, which prevent the toxin from attaching to neurons. Furthermore, the Hc domain is extensively studied as a non-toxic vaccine candidate and as a molecular vehicle for delivering therapeutic payloads specifically into the central nervous system.

Other names

Botulinum neurotoxin type B receptor-binding domainBoNT/B-HCBotulinum neurotoxin type B fragment CClostridium botulinum neurotoxin type B binding domain

The Hc domain serves as the primary target for neutralizing antibodies (antitoxins) which block the toxin's ability to bind to its neuronal receptors, Synaptotagmin I/II and gangliosides, thereby preventing cellular entry and subsequent paralysis.