1uvq

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{{STRUCTURE_1uvq| PDB=1uvq | SCENE= }}
 
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===CRYSTAL STRUCTURE OF HLA-DQ0602 IN COMPLEX WITH A HYPOCRETIN PEPTIDE===
 
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{{ABSTRACT_PUBMED_14769912}}
 
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==Disease==
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==Crystal structure of HLA-DQ0602 in complex with a hypocretin peptide==
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[[http://www.uniprot.org/uniprot/OREX_HUMAN OREX_HUMAN]] Defects in HCRT are the cause of narcolepsy type 1 (NRCLP1) [MIM:[http://omim.org/entry/161400 161400]]. Narcolepsy is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, such as cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. Note=Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients.<ref>PMID:10973318</ref>
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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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==Function==
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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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[[http://www.uniprot.org/uniprot/OREX_HUMAN OREX_HUMAN]] Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity.
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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 3 chain structure with sequence 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=1UVQ OCA].
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</div>
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<div class="pdbe-citations 1uvq" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Major histocompatibility complex|Major histocompatibility complex]]
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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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==Reference==
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*[[Orexin and Orexin receptor|Orexin and Orexin receptor]]
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<ref group="xtra">PMID:014769912</ref><references group="xtra"/><references/>
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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: Bell, J I.]]
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[[Category: Large Structures]]
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[[Category: Esnouf, R E.]]
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[[Category: Bell JI]]
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[[Category: Fugger, L.]]
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[[Category: Esnouf RE]]
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[[Category: Hansen, B E.]]
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[[Category: Fugger L]]
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[[Category: Harlos, K.]]
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[[Category: Hansen BE]]
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[[Category: Jones, E Y.]]
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[[Category: Harlos K]]
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[[Category: Siebold, C.]]
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[[Category: Jones EY]]
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[[Category: Strominger, J L.]]
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[[Category: Siebold C]]
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[[Category: Svejgaard, A.]]
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[[Category: Strominger JL]]
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[[Category: Wyer, J R.]]
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[[Category: Svejgaard A]]
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[[Category: Autoimmune disease]]
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[[Category: Wyer JR]]
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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 genomic]]
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[[Category: Structural proteomics in europe]]
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Current revision

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

PDB ID 1uvq

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