1et9
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CRYSTAL STRUCTURE OF THE SUPERANTIGEN SPE-H FROM STREPTOCOCCUS PYOGENES
OverviewOverview
Bacterial superantigens (SAgs) are a structurally related group of protein, toxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They, are implicated in a range of human pathologies associated with bacterial, infection whose symptoms result from SAg-mediated stimulation of a large, number (2-20%) of T-cells. At the molecular level, bacterial SAgs bind to, major histocompatability class II (MHC-II) molecules and disrupt the, normal interaction between MHC-II and T-cell receptors (TCRs). We have, determined high-resolution crystal structures of two newly identified, streptococcal superantigens, SPE-H and SMEZ-2. Both structures conform to, the generic bacterial superantigen folding pattern, comprising an OB-fold, N-terminal domain and a beta-grasp C-terminal domain. SPE-H and SMEZ-2, also display very similar zinc-binding sites on the outer concave surfaces, of their C-terminal domains. Structural comparisons with other SAgs, identify two structural sub-families. Sub-families are related by, conserved core residues and demarcated by variable binding surfaces for, MHC-II and TCR. SMEZ-2 is most closely related to the streptococcal SAg, SPE-C, and together they constitute one structural sub-family. In, contrast, SPE-H appears to be a hybrid whose N-terminal domain is most, closely related to the SEB sub-family and whose C-terminal domain is most, closely related to the SPE-C/SMEZ-2 sub-family. MHC-II binding for both, SPE-H and SMEZ-2 is mediated by the zinc ion at their C-terminal face, whereas the generic N-terminal domain MHC-II binding site found on many, SAgs appears not to be present. Structural comparisons provide evidence, for variations in TCR binding between SPE-H, SMEZ-2 and other members of, the SAg family; the extreme potency of SMEZ-2 (active at 10(-15) g ml-1, levels) is likely to be related to its TCR binding properties. The smez, gene shows allelic variation that maps onto a considerable proportion of, the protein surface. This allelic variation, coupled with the varied, binding modes of SAgs to MHC-II and TCR, highlights the pressure on SAgs, to avoid host immune defences.
About this StructureAbout this Structure
1ET9 is a Single protein structure of sequence from Streptococcus pyogenes. Full crystallographic information is available from OCA.
ReferenceReference
Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes., Arcus VL, Proft T, Sigrell JA, Baker HM, Fraser JD, Baker EN, J Mol Biol. 2000 May 26;299(1):157-68. PMID:10860729
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