| Primary Identifier | IPR022405 | Type | Domain |
| Short Name | Diphtheria_toxin_translocation |
| description | Diphtheria toxin () is a 58kDa 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 []. 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)diphthamideThe crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution []. The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the α+β type; a transmembrane (TM) domain, which consists of 9 α-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened β-barrel with a jelly-roll-like topology []. The TM- and receptor binding-domains together constitute fragment B.This entry represents the translocation domain (also known as the T domain) found as the central domain in 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 []. 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 [, ]. |
