1uvq

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[[Image:1uvq.jpg|left|200px]]<br /><applet load="1uvq" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1uvq, resolution 1.8&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HLA-DQ0602 IN COMPLEX WITH A HYPOCRETIN PEPTIDE'''<br />
 
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==Overview==
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==Crystal structure of HLA-DQ0602 in complex with a hypocretin peptide==
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The MHC class II molecule DQ0602 confers strong susceptibility to, narcolepsy but dominant protection against type 1 diabetes. The crystal, structure of DQ0602 reveals the molecular features underlying these, contrasting genetic properties. Structural comparisons to homologous DQ, molecules with differential disease associations highlight a previously, unrecognized interplay between the volume of the P6 pocket and the, specificity of the P9 pocket, which implies that presentation of an, expanded peptide repertoire is critical for dominant protection against, type 1 diabetes. In narcolepsy, the volume of the P4 pocket appears, central to the susceptibility, suggesting that the presentation of a, specific peptide population plays a major role.
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<StructureSection load='1uvq' size='340' side='right'caption='[[1uvq]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1uvq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UVQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uvq OCA], [https://pdbe.org/1uvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uvq RCSB], [https://www.ebi.ac.uk/pdbsum/1uvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uvq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/E9PMV2_HUMAN E9PMV2_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uv/1uvq_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1uvq ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The MHC class II molecule DQ0602 confers strong susceptibility to narcolepsy but dominant protection against type 1 diabetes. The crystal structure of DQ0602 reveals the molecular features underlying these contrasting genetic properties. Structural comparisons to homologous DQ molecules with differential disease associations highlight a previously unrecognized interplay between the volume of the P6 pocket and the specificity of the P9 pocket, which implies that presentation of an expanded peptide repertoire is critical for dominant protection against type 1 diabetes. In narcolepsy, the volume of the P4 pocket appears central to the susceptibility, suggesting that the presentation of a specific peptide population plays a major role.
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==Disease==
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Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy.,Siebold C, Hansen BE, Wyer JR, Harlos K, Esnouf RE, Svejgaard A, Bell JI, Strominger JL, Jones EY, Fugger L Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1999-2004. Epub 2004 Feb 9. PMID:14769912<ref>PMID:14769912</ref>
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Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]], Creutzfeldt-Jakob disease, variant, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]], Multiple sclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]], Narcolepsy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602358 602358]], Porphyria variegata OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600923 600923]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1UVQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=GLY:'>GLY</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:GLY+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UVQ OCA].
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</div>
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<div class="pdbe-citations 1uvq" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy., Siebold C, Hansen BE, Wyer JR, Harlos K, Esnouf RE, Svejgaard A, Bell JI, Strominger JL, Jones EY, Fugger L, Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1999-2004. Epub 2004 Feb 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14769912 14769912]
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*[[MHC 3D structures|MHC 3D structures]]
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*[[MHC II 3D structures|MHC II 3D structures]]
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*[[Orexin and Orexin receptor|Orexin and Orexin receptor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bell, J.I.]]
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[[Category: Bell JI]]
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[[Category: Esnouf, R.E.]]
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[[Category: Esnouf RE]]
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[[Category: Fugger, L.]]
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[[Category: Fugger L]]
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[[Category: Hansen, B.E.]]
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[[Category: Hansen BE]]
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[[Category: Harlos, K.]]
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[[Category: Harlos K]]
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[[Category: Jones, E.Y.]]
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[[Category: Jones EY]]
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[[Category: SPINE, Structural.Proteomics.in.Europe.]]
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[[Category: Siebold C]]
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[[Category: Siebold, C.]]
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[[Category: Strominger JL]]
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[[Category: Strominger, J.L.]]
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[[Category: Svejgaard A]]
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[[Category: Svejgaard, A.]]
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[[Category: Wyer JR]]
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[[Category: Wyer, J.R.]]
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[[Category: ACY]]
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[[Category: GLY]]
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[[Category: NAG]]
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[[Category: ZN]]
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[[Category: autoimmune disease]]
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[[Category: diabetes]]
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[[Category: immunology]]
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[[Category: mhc class ii]]
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[[Category: narcolepsy]]
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[[Category: spine]]
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[[Category: structural genomics]]
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[[Category: structural proteomics in europe]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:08:28 2008''
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Current revision

Crystal structure of HLA-DQ0602 in complex with a hypocretin peptide

PDB ID 1uvq

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