5c0b: Difference between revisions

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-'''Unreleased structure'''
-The entry 5c0b is ON HOLD  until Paper Publication
+==1E6 TCR in complex with HLA-A02 carrying RQFGPDFPTI==
+<StructureSection load='5c0b' size='340' side='right'caption='[[5c0b]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5c0b]] is a 10 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=5C0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C0B 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]] 2.03&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5c0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c0b OCA], [https://pdbe.org/5c0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c0b RCSB], [https://www.ebi.ac.uk/pdbsum/5c0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c0b ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://omim.org/entry/241600 241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref>   Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide-major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I-restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key-like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease.
-Authors: Rizkallah, P.J., Bulek, A.M., Cole, D.K., Sewell, A.K.
+Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity.,Cole DK, Bulek AM, Dolton G, Schauenberg AJ, Szomolay B, Rittase W, Trimby A, Jothikumar P, Fuller A, Skowera A, Rossjohn J, Zhu C, Miles JJ, Peakman M, Wooldridge L, Rizkallah PJ, Sewell AK J Clin Invest. 2016 May 16. pii: 85679. doi: 10.1172/JCI85679. PMID:27183389<ref>PMID:27183389</ref>
-Description: 1E6 TCR in complex with HLA-A02 carrying RQFGPDFPTI
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Bulek, A.M]]
+<div class="pdbe-citations 5c0b" style="background-color:#fffaf0;"></div>
-[[Category: Cole, D.K]]
-[[Category: Sewell, A.K]]
+==See Also==
-[[Category: Rizkallah, P.J]]
+*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
+*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bulek AM]]
+[[Category: Cole DK]]
+[[Category: Rizkallah PJ]]
+[[Category: Sewell AK]]