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2g9h
From Proteopedia
(New page: 200px<br /> <applet load="2g9h" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g9h, resolution 2.00Å" /> '''Crystal Structure o...) |
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| - | [[Image:2g9h.gif|left|200px]]<br /> | + | [[Image:2g9h.gif|left|200px]]<br /><applet load="2g9h" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2g9h" size=" | + | |
caption="2g9h, resolution 2.00Å" /> | caption="2g9h, resolution 2.00Å" /> | ||
'''Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule'''<br /> | '''Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Superantigens are bacterial or viral proteins that elicit massive T cell | + | Superantigens are bacterial or viral proteins that elicit massive T cell activation through simultaneous binding to major histocompatibility complex (MHC) class II and T cell receptors. This activation results in uncontrolled release of inflammatory cytokines, causing toxic shock. A remarkable property of superantigens, which distinguishes them from T cell receptors, is their ability to interact with multiple MHC class II alleles independently of MHC-bound peptide. Previous crystallographic studies have shown that staphylococcal and streptococcal superantigens belonging to the zinc family bind to a high affinity site on the class II beta-chain. However, the basis for promiscuous MHC recognition by zinc-dependent superantigens is not obvious, because the beta-chain is polymorphic and the MHC-bound peptide forms part of the binding interface. To understand how zinc-dependent superantigens recognize MHC, we determined the crystal structure, at 2.0 A resolution, of staphylococcal enterotoxin I bound to the human class II molecule HLA-DR1 bearing a peptide from influenza hemagglutinin. Interactions between the superantigen and DR1 beta-chain are mediated by a zinc ion, and 22% of the buried surface of peptide.MHC is contributed by the peptide. Comparison of the staphylococcal enterotoxin I.peptide.DR1 structure with ones determined previously revealed that zinc-dependent superantigens achieve promiscuous binding to MHC by targeting conservatively substituted residues of the polymorphic beta-chain. Additionally, these superantigens circumvent peptide specificity by engaging MHC-bound peptides at their conformationally conserved N-terminal regions while minimizing sequence-specific interactions with peptide residues to enhance cross-reactivity. |
==About this Structure== | ==About this Structure== | ||
| - | 2G9H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with ZN, SO4, EPE and DIO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2G9H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=EPE:'>EPE</scene> and <scene name='pdbligand=DIO:'>DIO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G9H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Fernandez, M | + | [[Category: Fernandez, M M.]] |
[[Category: Guan, R.]] | [[Category: Guan, R.]] | ||
| - | [[Category: Malchiodi, E | + | [[Category: Malchiodi, E L.]] |
| - | [[Category: Mariuzza, R | + | [[Category: Mariuzza, R A.]] |
[[Category: DIO]] | [[Category: DIO]] | ||
[[Category: EPE]] | [[Category: EPE]] | ||
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[[Category: zn]] | [[Category: zn]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:29:29 2008'' |
Revision as of 15:29, 21 February 2008
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Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule
Overview
Superantigens are bacterial or viral proteins that elicit massive T cell activation through simultaneous binding to major histocompatibility complex (MHC) class II and T cell receptors. This activation results in uncontrolled release of inflammatory cytokines, causing toxic shock. A remarkable property of superantigens, which distinguishes them from T cell receptors, is their ability to interact with multiple MHC class II alleles independently of MHC-bound peptide. Previous crystallographic studies have shown that staphylococcal and streptococcal superantigens belonging to the zinc family bind to a high affinity site on the class II beta-chain. However, the basis for promiscuous MHC recognition by zinc-dependent superantigens is not obvious, because the beta-chain is polymorphic and the MHC-bound peptide forms part of the binding interface. To understand how zinc-dependent superantigens recognize MHC, we determined the crystal structure, at 2.0 A resolution, of staphylococcal enterotoxin I bound to the human class II molecule HLA-DR1 bearing a peptide from influenza hemagglutinin. Interactions between the superantigen and DR1 beta-chain are mediated by a zinc ion, and 22% of the buried surface of peptide.MHC is contributed by the peptide. Comparison of the staphylococcal enterotoxin I.peptide.DR1 structure with ones determined previously revealed that zinc-dependent superantigens achieve promiscuous binding to MHC by targeting conservatively substituted residues of the polymorphic beta-chain. Additionally, these superantigens circumvent peptide specificity by engaging MHC-bound peptides at their conformationally conserved N-terminal regions while minimizing sequence-specific interactions with peptide residues to enhance cross-reactivity.
About this Structure
2G9H is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule., Fernandez MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA, J Biol Chem. 2006 Sep 1;281(35):25356-64. Epub 2006 Jul 6. PMID:16829512
Page seeded by OCA on Thu Feb 21 17:29:29 2008
Categories: Homo sapiens | Protein complex | Staphylococcus aureus | Fernandez, M M. | Guan, R. | Malchiodi, E L. | Mariuzza, R A. | DIO | EPE | SO4 | ZN | Hla clasii molecule | Immune system | Superantigen | Zn
