1eu3: Difference between revisions

Revision as of 13:31, 21 February 2008

CRYSTAL STRUCTURE OF THE SUPERANTIGEN SMEZ-2 (ZINC BOUND) 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

1EU3 is a Single protein structure of sequence from Streptococcus pyogenes with , and as ligands. 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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-[[Image:1eu3.jpg|left|200px]]<br /><applet load="1eu3" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1eu3.jpg|left|200px]]<br /><applet load="1eu3" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1eu3, resolution 1.68&Aring;" />
 '''CRYSTAL STRUCTURE OF THE SUPERANTIGEN SMEZ-2 (ZINC BOUND) FROM STREPTOCOCCUS PYOGENES'''<br />
 ==Overview==
-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.
+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 Structure==
-EU3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes] with PO4, ZN and K as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EU3 OCA].
+EU3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=K:'>K</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EU3 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Single protein]]
 [[Category: Streptococcus pyogenes]]
-[[Category: Arcus, V.L.]]
+[[Category: Arcus, V L.]]
-[[Category: Baker, E.N.]]
+[[Category: Baker, E N.]]
-[[Category: Baker, H.M.]]
+[[Category: Baker, H M.]]
-[[Category: Fraser, J.D.]]
+[[Category: Fraser, J D.]]
 [[Category: Proft, T.]]
-[[Category: Sigrell, J.A.]]
+[[Category: Sigrell, J A.]]
 [[Category: K]]
 [[Category: PO4]]
@@ Line 26: / Line 26: @@
 [[Category: superantigen fold]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:48:55 2007''
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