Tetanus neurotoxin heavy chain N-terminal fragment (TeNT-Hn)

Tetanus neurotoxin (TeNT) is a highly potent protein toxin produced by the bacterium Clostridium tetani, responsible for the life-threatening condition known as tetanus, which is characterized by spastic paralysis (StatPearls, 2023). The heavy-chain N-terminal fragment, often designated as the Hn domain, serves as the translocation machinery of the toxin (UniProt P04958). Following the binding of the C-terminal fragment to neuronal receptors and subsequent endocytosis, the Hn domain undergoes a pH-dependent conformational change within the acidic environment of the endosome (Pirazzini et al., 2017). This change allows the Hn fragment to insert into the endosomal membrane and form a channel through which the catalytic light chain is delivered into the cytosol. Once inside, the light chain cleaves vesicle-associated membrane protein 2 (VAMP2), preventing the release of inhibitory neurotransmitters (PubMed, PMC5033269). The Hn fragment is a critical target for neutralizing antibodies found in tetanus immune globulin and those elicited by the tetanus toxoid vaccine (Rossetto et al., 2014).

Other names

Hn domainTranslocation domain of tetanus toxinTetanus toxin heavy chain N-terminal fragment

Neutralization of toxin translocation into the neuronal cytosol by binding to the Hn domain.