1et9: Difference between revisions

|PDB= 1et9 |SIZE=350|CAPTION= <scene name='initialview01'>1et9</scene>, resolution 1.90&Aring;

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|LIGAND=  

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|RELATEDENTRY=[[1et6|1ET6]], [[1an8|1AN8]], [[1eu3|1EU3]], [[1eu4|1EU4]]

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1et9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1et9 OCA], [http://www.ebi.ac.uk/pdbsum/1et9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1et9 RCSB]</span>

 

 

==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.

 

1ET9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ET9 OCA].

 

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:[http://www.ncbi.nlm.nih.gov/pubmed/10860729 10860729]

[[Category: Single protein]]

[[Category: Arcus, V L.]]

[[Category: Baker, E N.]]

[[Category: Baker, H M.]]

[[Category: Fraser, J D.]]

[[Category: Proft, T.]]

[[Category: Sigrell, J A.]]