Homologous Superfamily

Diphtheria toxin, translocation domain superfamily (IPR036801)

Short name: Diphtheria_tox_transloc_sf

Overlapping entries


Diphtheria toxin (EC: is a 58 kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis [PMID: 8573568]. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows: NAD+ + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide

The crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution [PMID: 1589020]. The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the alpha + beta type; a transmembrane (TM) domain, which consists of 9 alpha-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened beta-barrel with a jelly-roll-like topology [PMID: 1589020]. The TM- and receptor binding-domains together constitute fragment B.

This entry represents the translocation domain (also known as the T domain) found in the middle of the Diphtheria toxin protein. The T domain has a multi-helical globin-like fold with two additional helices at N-termini, but which has no counterpart to the first globin helix. This domain is thought to unfold in the membrane [PMID: 7833807]. pH-induced conformational change in the T domain triggers insertion into the endosomal membrane and facilitates the transfer of the catalytic domain into the cytoplasm [PMID: 7833808, PMID: 8573568].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.