Structure of Shiga Toxins and Other AB 5 Toxins

Shiga toxins (Stx) are part of a general class of protein toxins referred to as AB5 holotoxins, including pertussis toxin, cholera toxin, E. coli heat-labile enterotoxins, and subtilase cytotoxin. The structural differences between the types and subtypes of Shiga toxins subtly influence the specificity and strength of binding of these toxins. There are two types of Shiga toxins, Stx1 and Stx2, each of which has multiple genetic variants. Each Shiga toxin has five identical B subunits that bind to gangliosides, such as the globotriaosylceramide (Gb3) on the surface of the target eukaryotic cell. The B subunits of Stx1 and Stx2 differ substantially from each other (62% identical), but within each of the Stx1 or Sxt2 types, the B subunits are more than 80% identical. The A subunits of Stx1 and Stx2 have the same enzymatic activity, but are less than 60% identical. The A1 domain of the A subunit is released by an intracellular protease, and its specific N-glycosidase can then inactivate the 60S subunit of ribosomes. A single holotoxin molecule that is properly delivered and processed is sufficient to kill a target cell by inhibiting protein synthesis.