7n2p: Difference between revisions
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==AS4.3-RNASEH2b-HLA*B27== | |||
<StructureSection load='7n2p' size='340' side='right'caption='[[7n2p]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7n2p]] is a 5 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=7N2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N2P 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7n2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n2p OCA], [https://pdbe.org/7n2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n2p RCSB], [https://www.ebi.ac.uk/pdbsum/7n2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n2p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A3F718_HUMAN A3F718_HUMAN] Involved in the presentation of foreign antigens to the immune system.[ARBA:ARBA00002297] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))(1). How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8(+) T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public beta-chain variable region-complementary-determining region 3beta (BV9-CDR3beta) motif(2-4) from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent alpha-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3beta TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease. | |||
Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.,Yang X, Garner LI, Zvyagin IV, Paley MA, Komech EA, Jude KM, Zhao X, Fernandes RA, Hassman LM, Paley GL, Savvides CS, Brackenridge S, Quastel MN, Chudakov DM, Bowness P, Yokoyama WM, McMichael AJ, Gillespie GM, Garcia KC Nature. 2022 Dec;612(7941):771-777. doi: 10.1038/s41586-022-05501-7. Epub 2022 , Dec 7. PMID:36477533<ref>PMID:36477533</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7n2p" style="background-color:#fffaf0;"></div> | ||
[[Category: Jude | |||
[[Category: | ==See Also== | ||
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]] | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Garcia KC]] | |||
[[Category: Jude KM]] | |||
[[Category: Yang X]] | |||
Latest revision as of 14:13, 23 October 2024
AS4.3-RNASEH2b-HLA*B27AS4.3-RNASEH2b-HLA*B27
Structural highlights
FunctionA3F718_HUMAN Involved in the presentation of foreign antigens to the immune system.[ARBA:ARBA00002297] Publication Abstract from PubMedHuman leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))(1). How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8(+) T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public beta-chain variable region-complementary-determining region 3beta (BV9-CDR3beta) motif(2-4) from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent alpha-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3beta TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease. Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.,Yang X, Garner LI, Zvyagin IV, Paley MA, Komech EA, Jude KM, Zhao X, Fernandes RA, Hassman LM, Paley GL, Savvides CS, Brackenridge S, Quastel MN, Chudakov DM, Bowness P, Yokoyama WM, McMichael AJ, Gillespie GM, Garcia KC Nature. 2022 Dec;612(7941):771-777. doi: 10.1038/s41586-022-05501-7. Epub 2022 , Dec 7. PMID:36477533[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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