2ypl

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{{STRUCTURE_2ypl| PDB=2ypl | SCENE= }}
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==Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms==
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===Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms===
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<StructureSection load='2ypl' size='340' side='right' caption='[[2ypl]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23161907}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2ypl]] is a 5 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=2YPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YPL FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ypk|2ypk]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ypl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ypl RCSB], [http://www.ebi.ac.uk/pdbsum/2ypl PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://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>
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== Function ==
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[[http://www.uniprot.org/uniprot/1B57_HUMAN 1B57_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Polymorphic differences distinguishing MHC class I subtypes often permit the presentation of shared epitopes in conformationally identical formats but can affect T-cell repertoire selection, differentially impacting autoimmune susceptibilities and viral clearance in vivo. The molecular mechanisms underlying this effect are not well understood. We performed structural, thermodynamic, and functional analyses of a conserved T-cell receptor (TCR) which is frequently expanded in response to a HIV-1 epitope when presented by HLA-B*5701 but is not selected by HLA-B*5703, which differs from HLA-B*5701 by two concealed polymorphisms. Our findings illustrate that although both HLA-B*57 subtypes display the epitope in structurally conserved formats, the impact of their polymorphic differences occurs directly as a consequence of TCR ligation, primarily because of peptide adjustments required for TCR binding, which involves the interplay of polymorphic residues and water molecules. These minor differences culminate in subtype-specific differential TCR-binding kinetics and cellular function. Our data demonstrate a potential mechanism whereby the most subtle MHC class I micropolymorphisms can influence TCR use and highlight their implications for disease outcomes.
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==Disease==
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Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms.,Stewart-Jones GB, Simpson P, van der Merwe PA, Easterbrook P, McMichael AJ, Rowland-Jones SL, Jones EY, Gillespie GM Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):E3483-92. doi:, 10.1073/pnas.1207896109. Epub 2012 Nov 16. PMID:23161907<ref>PMID:23161907</ref>
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[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/1B57_HUMAN 1B57_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://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.
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</div>
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==About this Structure==
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[[2ypl]] is a 5 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=2YPL OCA].
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==See Also==
==See Also==
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[T-cell receptor|T-cell receptor]]
*[[T-cell receptor|T-cell receptor]]
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== References ==
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==Reference==
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<references/>
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<references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Easterbrook, P.]]
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[[Category: Easterbrook, P]]
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[[Category: Gillespie, G M.]]
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[[Category: Gillespie, G M]]
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[[Category: Jones, E Y.]]
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[[Category: Jones, E Y]]
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[[Category: Mcmichael, A J.]]
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[[Category: Mcmichael, A J]]
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[[Category: Merwe, P A.Van Der.]]
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[[Category: Merwe, P A.Van Der]]
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[[Category: Rowland-Jones, S L.]]
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[[Category: Rowland-Jones, S L]]
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[[Category: Simpson, P.]]
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[[Category: Simpson, P]]
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[[Category: Stewart-Jones, G B.]]
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[[Category: Stewart-Jones, G B]]
[[Category: Immune system-viral protein complex]]
[[Category: Immune system-viral protein complex]]
[[Category: Micropolymorphism]]
[[Category: Micropolymorphism]]

Revision as of 14:04, 18 December 2014

Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms

2ypl, resolution 2.40Å

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