Comparative three-dimensional structure of bacterial superantigenic toxins

From the first three-dimensional structure of a bacterial superantigen to the complexes of these toxins with their receptors the complete archaeology of these molecules has been mapped and a wealth of information has been obtained. The ability to assign specific functions to discrete regions of the toxin and to assess the roles of individual amino acid residues by a combination of mutagenesis and structural techniques has enabled detailed comparisons of the entire bacterial superantigen family of proteins. Superantigens are powerful T cell stimulatory molecules produced primarily by Staphylococcus aureus and Streptococcus pyogenes. The action of these toxins as SAgs can be attributed to their ability to cross-link MHC class II molecules and T cell receptors to form a trimolecular complex. The number of known bacterial proteins with superantigenic properties and/or high homology with known SAgs has grown considerably over the last decade. Staphylococcal enterotoxins (SEs), A, B, Cl-3, D, E, H, I, J; toxic shock syndrome toxin-1 (TSST-1), the streptococcal pyrogenic exotoxins (Spes) A, C, H; and streptococcal mitogenic exotoxin SME-Z₂ and streptococcal superantigen (SSA) are the most well studied bacterial SAgs to date. Other pathogens, such as Mycoplasma arthritidis and Yersinia enterocolitica have also been shown to secrete superantigenic proteins and the characterization of these toxins has recently been helped by the elucidation of their crystal structures.