MOLECULAR-STRUCTURE OF STAPHYLOCOCCUS AND STREPTOCOCCUS SUPERANTIGENS

Staphylococcus aureus and streptococci, notably those belonging to gro up A, make up a large family of true exotoxins referred to as pyrogeni c toxin superantigens. These toxins cause toxic shock-like syndromes a nd have been implicated in several allergic and autoimmune diseases. I ncluded within this group of proteins are the staphylococcal enterotox ins, designated serotypes A, B, Cn, D, E, and G; two forms of toxic sh ock syndrome toxin-1 also made by Staphylococcus aureus; the group A s treptococcal pyrogenic exotoxins, serotypes A, B, and C; and recently described toxins associated with groups B, C, F, and G streptococci. T he nucleotide sequences of the genes for all of the toxins except thos e from the groups B, C, F, and G streptococcal strains have been seque nced. The sequencing studies indicate that staphylococcal enterotoxins B and C and streptococcal pyrogenic exotoxin A share highly significa nt sequence similarity; staphylococcal enterotoxins A, D, and E share highly significant sequence similarity; and toxic shock syndrome toxin -1 and streptococcal pyrogenic exotoxin B and C share little, if any, sequence similarity with any of the toxins. Despite the dissimilaritie s seen in primary amino acid sequence among some members of the toxin family, it was hypothesized that there was likely to be significant th ree-dimensional structure similarity among all the toxins. The three-d imensional structures of three of the pyrogenic toxin superantigens ha ve been determined recently. The structural features of two of these, toxic shock syndrome toxin-1 and enterotoxin C3, are presented. Toxic shock syndrome-1 exists as a protein with two major domains, referred to as A and B. The molecule begins with a short N-terminal alpha-helix that then lends into a clawshaped structure in domain B that is made up of beta strands. Domain B is connected to domain A by a central dia gonal alpha-helix of amino acids which are important in both the super antigenic and the lethal activities of the toxin. Finally, domain A co ntains a wall of beta strands and the C terminus of the molecule. The small N-terminal alpha-helix and the two beta sheet structures (claw a nd wall) form part of a deep groove on the back side of the toxin that contains the central alpha-helix. Staphylococcal enterotoxin C3 diffe rs somewhat from toxic shock syndrome toxin-1: it has an elongated N t erminus that folds over domain A, an alpha-helix at the base of domain B, a cysteine loop structure above the claw structure in domain B of toxic shock syndrome toxin-1, and a second central alpha-helix.