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| {{STRUCTURE_1seb| PDB=1seb | SCENE= }}
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| ===COMPLEX OF THE HUMAN MHC CLASS II GLYCOPROTEIN HLA-DR1 AND THE BACTERIAL SUPERANTIGEN SEB===
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| {{ABSTRACT_PUBMED_8152483}}
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| ==Disease== | | ==COMPLEX OF THE HUMAN MHC CLASS II GLYCOPROTEIN HLA-DR1 AND THE BACTERIAL SUPERANTIGEN SEB== |
| [[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1) [MIM:[http://omim.org/entry/181000 181000]]. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.<ref>PMID:14508706</ref> | | <StructureSection load='1seb' size='340' side='right'caption='[[1seb]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1seb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SEB FirstGlance]. <br> |
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1seb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1seb OCA], [https://pdbe.org/1seb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1seb RCSB], [https://www.ebi.ac.uk/pdbsum/1seb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1seb ProSAT]</span></td></tr> |
| | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/ETXB_STAAU ETXB_STAAU] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death. |
| | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> |
| | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/se/1seb_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> |
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1seb ConSurf]. |
| | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == |
| | The structure of a bacterial superantigen, Staphylococcus aureus enterotoxin B, bound to a human class II histocompatibility complex molecule (HLA-DR1) has been determined by X-ray crystallography. The superantigen binds as an intact protein outside the conventional peptide antigen-binding site of the class II major histocompatibility complex (MHC) molecule. No large conformational changes occur upon complex formation in either the DR1 or the enterotoxin B molecules. The structure of the complex helps explain how different class II molecules and superantigens associate and suggests a model for ternary complex formation with the T-cell antigen receptor (TCR), in which unconventional TCR-MHC contacts are possible. |
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| ==Function==
| | Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen.,Jardetzky TS, Brown JH, Gorga JC, Stern LJ, Urban RG, Chi YI, Stauffacher C, Strominger JL, Wiley DC Nature. 1994 Apr 21;368(6473):711-8. PMID:8152483<ref>PMID:8152483</ref> |
| [[http://www.uniprot.org/uniprot/ETXB_STAAU ETXB_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death. [[http://www.uniprot.org/uniprot/DRA_HUMAN DRA_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [[http://www.uniprot.org/uniprot/2B11_HUMAN 2B11_HUMAN]] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.
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| ==About this Structure==
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| [[1seb]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEB OCA].
| | </div> |
| | <div class="pdbe-citations 1seb" style="background-color:#fffaf0;"></div> |
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| ==See Also== | | ==See Also== |
| *[[Major histocompatibility complex|Major histocompatibility complex]] | | *[[MHC 3D structures|MHC 3D structures]] |
| | | *[[MHC II 3D structures|MHC II 3D structures]] |
| ==Reference== | | == References == |
| <ref group="xtra">PMID:008152483</ref><references group="xtra"/><references/>
| | <references/> |
| | __TOC__ |
| | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] |
| [[Category: Staphylococcus aureus]] | | [[Category: Staphylococcus aureus]] |
| [[Category: Brown, J H.]] | | [[Category: Brown JH]] |
| [[Category: Chi, Y I.]] | | [[Category: Chi YI]] |
| [[Category: Gorga, J C.]] | | [[Category: Gorga JC]] |
| [[Category: Jardetzky, T S.]] | | [[Category: Jardetzky TS]] |
| [[Category: Stauffacher, C.]] | | [[Category: Stauffacher C]] |
| [[Category: Stern, L J.]] | | [[Category: Stern LJ]] |
| [[Category: Strominger, J L.]] | | [[Category: Strominger JL]] |
| [[Category: Urban, R G.]] | | [[Category: Urban RG]] |
| [[Category: Wiley, D C.]] | | [[Category: Wiley DC]] |
| [[Category: Enterotoxin peptide]]
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| [[Category: Histocompatibility antigen]]
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| [[Category: Mhc ii]]
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| [[Category: Superantigen]]
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| [[Category: Toxin]]
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