CRYSTAL-STRUCTURE OF THE SUPERANTIGEN STAPHYLOCOCCAL-ENTEROTOXIN TYPE-A

Staphylococcal enterotoxins are prototype superantigens characterized by their ability to bind to major histocompatibility complex (MHC) cla ss II molecules and subsequently activate a large fraction of T-lympho cytes, The crystal structure of staphylococcal enterotoxin type A (SEA ), a 27 kDa monomeric protein, was determined to 1.9 Angstrom resoluti on with an R-factor of 19.9% by multiple isomorphous replacement, SEA is a two domain protein composed of a beta-barrel and a beta-grasp mot if demonstrating the same general structure as staphylococcal enteroto xins SEB and TSST-1. Unique for SEA, however, is a Zn2+ coordination s ite involved in MHC class II binding, Four amino acids including Ser1, His187, His225 and Asp227 were found to be involved in direct coordin ation of the metal ion, SEA is the first Zn2+ binding enterotoxin that has been structurally determined.