Molecular structure of staphylococcus and streptococcus superantigens

Staphylococcus aureus and streptococci, notably those belonging to group A, make up a large family of true exotoxins referred to as pyrogenic toxin superantigens. These toxins cause toxic shock-like syndromes and have been implicated in several allergic and autoimmune diseases. Included within this group of proteins are the staphylococcal enterotoxins, designated serotypes A, B, Cn, D, E, and G; two forms of toxic shock syndrome toxin-1 also made by Staphylococcus aureus; the group A streptococcal pyrogenic exotoxins, serotypes A, B, and C; and recently described toxins associated with groups B, C, F, and G streptococci. The nucleotide sequences of the genes for all of the toxins except those from the groups B, C, F, and G streptococcal strains have been sequenced. The sequencing studies indicate that staphylococcal enterotoxins B and C and streptococcal pyrogenic exotoxin A share highly significant 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 dissimilarities seen in primary amino acid sequence among some members of the toxin family, it was hypothesized that there was likely to be significant three-dimensional structure similarity among all the toxins. The three-dimensional structures of three of the pyrogenic toxin superantigens have 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 α-helix that then leads into a clawshaped structure in domain B that is made up of β strands. Domain B is connected to domain A by a central diagonal α-helix of amino acids which are important in both the superantigenic and the lethal activities of the toxin. Finally, domain A contains a wall of β strands and the C terminus of the molecule. The small N-terminal α-helix and the two β sheet structures (claw and wall) form part of a deep groove on the back side of the toxin that contains the central α-helix. Staphylococcal enterotoxin C3 differs somewhat from toxic shock syndrome toxin-1: it has an elongated N terminus that folds over domain A, an α-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 α-helix.