A structural and functional comparison of staphylococcal enterotoxins A and C2 reveals remarkable similarity and dissimilarity

Staphylococcal enterotoxins and toxic shock syndrome toxin-1 are known as superantigens due to their ability to activate a large number of T-cells by crosslinking the major histocompatibility complex class II molecules with the T-cell receptor. Although superantigens seem to act by a common mechanism, they vary in many of their specific interactions and biological properties. A structural comparison of staphylococcal enterotoxins A and C2, members of the staphylococcal superantigens, has shown large conformational differences at the putative TcR interaction site (loops between αN-α2, α4-β9 and β10-α5 in staphylococcal enterotoxin A) that could explain the variability in their T-cell receptor specificity. A common Zn²⁺-binding site was identified in both staphylococcal enterotoxin A and C2 that is superimposable but differs somewhat in its coordination geometry between the two molecules.