3skn

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<StructureSection load='3skn' size='340' side='right'caption='[[3skn]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
<StructureSection load='3skn' size='340' side='right'caption='[[3skn]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3skn]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SKN FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3skn]] is a 8 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=3SKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SKN FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1mi5|1mi5]], [[1kgc|1kgc]], [[1m05|1m05]], [[3ffc|3ffc]], [[3sjv|3sjv]], [[3skm|3skm]], [[3sko|3sko]]</div></td></tr>
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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]] 2.9&#8491;</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=3skn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3skn OCA], [https://pdbe.org/3skn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3skn RCSB], [https://www.ebi.ac.uk/pdbsum/3skn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3skn ProSAT]</span></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=3skn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3skn OCA], [https://pdbe.org/3skn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3skn RCSB], [https://www.ebi.ac.uk/pdbsum/3skn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3skn ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Disease ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/TRAC_HUMAN TRAC_HUMAN] TCR-alpha-beta-positive T-cell deficiency. The disease is caused by variants affecting the gene represented in this entry.
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EBV is a ubiquitous and persistent human pathogen, kept in check by the cytotoxic T cell response. In this study, we investigated how three TCRs, which differ in their T cell immunodominance hierarchies and gene usage, interact with the same EBV determinant (FLRGRAYGL), bound to the same Ag-presenting molecule, HLA-B8. We found that the three TCRs exhibit differing fine specificities for the viral Ag. Further, via structural and biophysical approaches, we demonstrated that the viral Ag provides the greatest energetic contribution to the TCR-peptide-HLA interaction, while focusing on a few adjacent HLA-based interactions to further tune fine-specificity requirements. Thus, the TCR engages the peptide-HLA with the viral Ag as the main glue, such that neighboring TCR-MHC interactions are recruited as a supportive adhesive. Collectively, we provide a portrait of how the host's adaptive immune response differentially engages a common viral Ag.
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== Function ==
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[https://www.uniprot.org/uniprot/TRAC_HUMAN TRAC_HUMAN] Constant region of T cell receptor (TR) alpha chain (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585).<ref>PMID:15040585</ref> <ref>PMID:23524462</ref> <ref>PMID:24600447</ref> <ref>PMID:25493333</ref>
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A structural basis for varied alphabeta TCR usage against an immunodominant EBV antigen restricted to a HLA-B8 molecule.,Gras S, Wilmann PG, Chen Z, Halim H, Liu YC, Kjer-Nielsen L, Purcell AW, Burrows SR, McCluskey J, Rossjohn J J Immunol. 2012 Jan 1;188(1):311-21. Epub 2011 Dec 2. PMID:22140258<ref>PMID:22140258</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3skn" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Burrows, S R]]
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[[Category: Burrows SR]]
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[[Category: Chih, L Yu]]
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[[Category: Gras S]]
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[[Category: Gras, S]]
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[[Category: Hanim H]]
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[[Category: Hanim, H]]
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[[Category: Kjer-Nielsen L]]
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[[Category: Kjer-Nielsen, L]]
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[[Category: Mccluskey J]]
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[[Category: Mccluskey, J]]
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[[Category: Purcell AW]]
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[[Category: Purcell, A W]]
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[[Category: Rossjohn J]]
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[[Category: Rossjohn, J]]
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[[Category: Wilmann PG]]
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[[Category: Wilmann, P G]]
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[[Category: Yu Chih L]]
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[[Category: Zhenjun, C]]
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[[Category: Zhenjun C]]
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[[Category: Immune system]]
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[[Category: T cell receptor]]
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Revision as of 12:59, 14 March 2024

Crystal structure of the RL42 TCR unliganded

PDB ID 3skn

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