Tetanus neurotoxin heavy chain C-terminal domain (Hc-TeTx)

The **tetanus neurotoxin heavy chain C-terminal domain** (Hc-TeTx) is a ~50 kDa domain of the larger tetanus neurotoxin (TeNT) produced by *Clostridium tetani*. TeNT consists of a light chain with zinc-protease activity and a heavy chain comprising two domains: the N-terminal (translocation) and the C-terminal (binding) domains[1][6]. The C-terminal domain is responsible for the highly selective binding of the neurotoxin to neural cell surface receptors—primarily polysialogangliosides (such as GD2, GD1b, and GT1b)—and a specific, possibly GPI-anchored protein, allowing entry into neurons and retrograde transport to the spinal cord[2][1][3][6]. While the full toxin is the causative agent of spastic paralysis (tetanus), the **Hc-TeTx domain itself** is being investigated as a vehicle for neuronal delivery and for its potential neuroprotective effects in neurodegenerative disease models such as amyotrophic lateral sclerosis, independent of the neurotoxin’s paralytic enzyme activity[3]. The domain’s high affinity and specificity for neurons make it an attractive scaffold for engineering targeted therapies or imaging agents, though its clinical application is limited primarily by concerns of immunogenicity and molecular safety (in the absence of catalytic LC activity)[3][1].

Other names

Hc-TeTxTeNT-HC (less common)Carboxyl-terminal domain of tetanus toxin heavy chain

Mediates binding of tetanus neurotoxin to motor neuron terminals and internalization via ganglioside (and putative protein) receptor interaction[2][1]; Enables neurotrophin-like, PI3K/Akt pathway modulation for neuroprotection in preclinical models[3]