{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:54:14Z","timestamp":1773338054268,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,4,10]],"date-time":"2007-04-10T00:00:00Z","timestamp":1176163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The illnesses associated with bacterial superantigens (SAgs) such as food poisoning and toxic shock syndrome, as well as the emerging threat of purpura fulminans and community\u2010associated methicillin\u2010resistant <jats:italic>S. aureus<\/jats:italic> producer of SAgs, emphasize the importance of a better characterization of SAg binding to their natural ligands, which would allow the development of drugs or biological reagents able to neutralize their action. SAgs are toxins that bind major histocompatibility complex class II molecules (MHC\u2010II) and T\u2010cell receptors (TCR), in a nonconventional manner, inducing T\u2010cell activation that leads to production of cytokines such as tumor necrosis factor and interleukin\u20102, which may result in acute toxic shock. Previously, we cloned and expressed a new natural variant of staphylococcal enterotoxin G (SEG) and evaluated its ability to stimulate <jats:italic>in vivo<\/jats:italic> murine T\u2010cell subpopulations. We found an early, strong, and widespread stimulation of mouse V\u03b28.2 T\u2010cells when compared with other SAgs member of the SEB subfamily. In search for the reason of the strong mitogenic potency, we determined the SEG crystal structure by X\u2010ray crystallography to 2.2 \u00c5 resolution and analyzed SEG binding to mV\u03b28.2 and MHC\u2010II. Calorimetry and SPR analysis showed that SEG has an affinity for mV\u03b28.2 40 to 100\u2010fold higher than that reported for other members of SEB subfamily, and the highest reported for a wild type SAg\u2010TCR couple. We also found that mutations introduced in mV\u03b28.2 to produce a high affinity mutant for other members of the SEB subfamily do not greatly affect binding to SEG. Crystallographic analysis and docking into mV\u03b28.2 in complex with SEB, SEC3, and SPEA showed that the deletions and substitution of key amino acids remodeled the putative surface of the mV\u03b28.2 binding site without affecting the binding to MHC\u2010II. This results in a SAg with improved binding to its natural ligands, which may confer a possible evolutionary advantage for bacterial strains expressing SEG. Proteins 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.21388","type":"journal-article","created":{"date-parts":[[2007,4,10]],"date-time":"2007-04-10T23:17:10Z","timestamp":1176247030000},"page":"389-402","source":"Crossref","is-referenced-by-count":20,"title":["Superantigen natural affinity maturation revealed by the crystal structure of staphylococcal enterotoxin G and its binding to T\u2010cell receptor V\u03b28.2"],"prefix":"10.1002","volume":"68","author":[{"given":"Marisa M.","family":"Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suparna","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio C.","family":"De Marzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick 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