1h15: Difference between revisions

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-{{Seed}}
-[[Image:1h15.png|left|200px]]
-<!--
+==X-ray crystal structure of HLA-DRA1*0101/DRB5*0101 complexed with a peptide from Epstein Barr Virus DNA polymerase==
-The line below this paragraph, containing "STRUCTURE_1h15", creates the "Structure Box" on the page.
+<StructureSection load='1h15' size='340' side='right'caption='[[1h15]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1h15]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_4 Human gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H15 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-{{STRUCTURE_1h15|  PDB=1h15  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h15 OCA], [https://pdbe.org/1h15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h15 RCSB], [https://www.ebi.ac.uk/pdbsum/1h15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h15 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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.
+== 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/h1/1h15_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=1h15 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases.
-===X-RAY CRYSTAL STRUCTURE OF HLA-DRA1*0101/DRB5*0101 COMPLEXED WITH A PEPTIDE FROM EPSTEIN BARR VIRUS DNA POLYMERASE===
+A functional and structural basis for TCR cross-reactivity in multiple sclerosis.,Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P, Sondergaard L, Svejgaard A, Wucherpfennig K, Stuart DI, Bell JI, Jones EY, Fugger L Nat Immunol. 2002 Oct;3(10):940-3. Epub 2002 Sep 3. PMID:12244309<ref>PMID:12244309</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1h15" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12244309}}, adds the Publication Abstract to the page
+*[[MHC 3D structures|MHC 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12244309 is the PubMed ID number.
+*[[MHC II 3D structures|MHC II 3D structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_12244309}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-H15 is a 6 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H15 OCA].
-==Reference==
-<ref group="xtra">PMID:12244309</ref><references group="xtra"/>
-[[Category: DNA-directed DNA polymerase]]
 [[Category: Homo sapiens]]
-[[Category: Andersson, C.]]
+[[Category: Human gammaherpesvirus 4]]
-[[Category: Bell, J I.]]
+[[Category: Large Structures]]
-[[Category: Fugger, L.]]
+[[Category: Andersson C]]
-[[Category: Harlos, K.]]
+[[Category: Bell JI]]
-[[Category: Hjorth, P.]]
+[[Category: Fugger L]]
-[[Category: Ikemizu, S.]]
+[[Category: Harlos K]]
-[[Category: Jacobsen, H.]]
+[[Category: Hjorth P]]
-[[Category: Jones, E Y.]]
+[[Category: Ikemizu S]]
-[[Category: Lang, H.]]
+[[Category: Jacobsen H]]
-[[Category: Madsen, L.]]
+[[Category: Jones EY]]
-[[Category: Sondergaard, L.]]
+[[Category: Lang H]]
-[[Category: Stuart, D I.]]
+[[Category: Madsen L]]
-[[Category: Svejgaard, A.]]
+[[Category: Sondergaard L]]
-[[Category: Wucherpfennig, K.]]
+[[Category: Stuart DI]]
-[[Category: Class ii]]
+[[Category: Svejgaard A]]
-[[Category: Dna polymerase]]
+[[Category: Wucherpfennig K]]
-[[Category: Dna-directed dna polymerase]]
-[[Category: Dr2]]
-[[Category: Drb5]]
-[[Category: Ebv]]
-[[Category: Hla]]
-[[Category: Immune system]]
-[[Category: Mhc]]
-[[Category: Peptide]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 08:28:50 2009''