Diphtheria toxin (DT) (DT)

Diphtheria toxin (DT) is a 535-amino acid exotoxin secreted by Corynebacterium diphtheriae and is the primary virulence factor responsible for the disease diphtheria [4, 9]. It is organized into two main fragments: Fragment A, which possesses catalytic activity, and Fragment B, which contains the translocation (T) and receptor-binding (R) domains [3, 8]. The R-domain of Fragment B specifically recognizes and binds to the Heparin-binding EGF-like growth factor (HB-EGF) on the surface of susceptible host cells, facilitating the toxin's entry via receptor-mediated endocytosis [7, 10]. Once inside the endosome, the T-domain undergoes a conformational change that allows Fragment A to be translocated into the cytoplasm, where it halts protein synthesis by ADP-ribosylating elongation factor 2 (EF-2) [3, 4]. Therapeutic strategies primarily focus on neutralizing Fragment B using Diphtheria Antitoxin (DAT) or preventing its action through vaccination with diphtheria toxoid, which induces protective antibodies against the toxin's binding and translocation domains [10, 13]. Additionally, the high affinity of Fragment B for HB-EGF has been exploited in the development of targeted cancer therapies and as a tool for studying growth factor signaling [5, 8].

Other names

Corynebacterium diphtheriae exotoxinFragment BDiphtheria toxin receptor-binding domainCRM197DTxCorynebacterium diphtheriae exotoxin, fragment B at HB-EGF binding site

Neutralization of the receptor-binding domain (Fragment B) to prevent cellular entry and subsequent inhibition of protein synthesis.