title: Identification of a secondary zinc-binding site in staphylococcal enterotoxin C2. Implications for superantigen recognition.
abstract: The previously determined crystal structure of the superantigen staphylococcal enterotoxin C2 (SEC2) showed binding of a single zinc ion located between the N- and C-terminal domains. Here we present the crystal structure of SEC2 determined to 2.0 A resolution in the presence of additional zinc. The structure revealed the presence of a secondary zinc-binding site close to the major histocompatibility complex (MHC)-binding site of the toxin and some 28 A away from the primary zinc-binding site of the toxin found in previous studies. T cell stimulation assays showed that varying the concentration of zinc ions present affected the activity of the toxin and we observed that high zinc concentrations considerably inhibited T cell responses. This indicates that SEC2 may have multiple modes of interaction with the immune system that are dependent on serum zinc levels. The potential role of the secondary zinc-binding site and that of the primary one in the formation of the TCR.SEC2.MHC complex are considered, and the possibility that zinc may regulate the activity of SEC2 as a toxin facilitating different T cell responses is discussed.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Anastassios C
authors.initials: AC
authors.lastname: Papageorgiou
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Baker
authors.forename: Julie D
authors.initials: JD
authors.lastname: McLeod
authors.forename: Sayed K
authors.initials: SK
authors.lastname: Goda
authors.forename: Claire N
authors.initials: CN
authors.lastname: Manzotti
authors.forename: David M
authors.initials: DM
authors.lastname: Sansom
authors.forename: Howard S
authors.initials: HS
authors.lastname: Tranter
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry; D001665:Binding Sites; D016466:CHO Cells; D002455:Cell Division; D006224:Cricetinae; D018360:Crystallography, X-Ray; D019281:Dimerization; D004768:Enterotoxins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry*
chemical_list: D000942:Antigens, Bacterial; D004768:Enterotoxins; C034959:enterotoxin C, staphylococcal; D015032:Zinc