Tetanus toxin heavy chain C-terminal domain (TeNT-Hc) (TeNT-Hc)

The Tetanus toxin heavy chain C-terminal domain (TeNT-Hc), also known as Fragment C, is a 50 kDa protein domain derived from the tetanus neurotoxin produced by Clostridium tetani (UniProt P04958). It serves as the primary receptor-binding component, facilitating the toxin's attachment to the presynaptic membrane of motor neurons through a dual-receptor mechanism involving polysialogangliosides (GD1b, GT1b) and protein receptors such as nidogen-1 and nidogen-2 (Bercsenyi et al., 2014). Following binding, TeNT-Hc mediates the internalization and retrograde axonal transport of the toxin to the spinal cord, a process critical for the pathogenesis of tetanus (Lalli et al., 2003). In clinical practice, this domain is the target of neutralizing antibodies induced by the tetanus toxoid vaccine and those provided by tetanus immune globulin (StatPearls, 2023). Beyond its role in disease, TeNT-Hc is extensively utilized in biomedical research as a non-toxic molecular vehicle for delivering therapeutic agents, such as enzymes or genetic material, directly into the central nervous system (Rossetto et al., 2014). Its high affinity for neurons and ability to bypass the blood-brain barrier via retrograde transport make it a significant tool for treating neurodegenerative conditions in experimental models.

Other names

Fragment CTTCTeNT-HcTetanus toxin Hc fragmentTetanus toxin receptor-binding domain

Neutralization of the binding domain to prevent neuronal entry and retrograde transport.