THE STRUCTURE OF THE SUPERANTIGEN EXFOLIATIVE TOXIN-A SUGGESTS A NOVEL REGULATION AS A SERINE-PROTEASE

Exfoliative toxin A (ETA) causes staphylococcal scalded skin syndrome which is characterized by a specific intraepidermal separation of laye rs of the skin. The mechanism by which ETA causes skin separation is u nknown although protease or superantigen activity has been implicated. The X-ray crystal structure of ETA has been solved in two crystal for ms to 2.1 and 2.3 Angstrom resolution and R-factors of 17% and 19%, re spectively. The structures indicate that ETA belongs to the chymotryps in-like family of serine proteases and cleaves substrates after acidic residues. The conformation of a loop adjacent to the catalytic site i s suggested to be key in regulating the proteolytic activity of ETA th rough controlling whether the main chain carbonyl group of Pro192 occu pies the oxyanion hole. A unique amino-terminal domain containing a 15 -residue amphipathic alpha helix may also be involved in protease acti vation through binding a specific receptor. Substitution of the active site serine residue with cysteine abolishes the ability of ETA to pro duce the characteristic separation of epidermal layers but not its abi lity to induce T cell proliferation.