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==Crystal Structures of High Affinity Human T-Cell Receptors Bound to pMHC RevealNative Diagonal Binding Geometry Unbound TCR Clone 5-1==
==Crystal Structures of High Affinity Human T-Cell Receptors Bound to pMHC RevealNative Diagonal Binding Geometry Unbound TCR Clone 5-1==
<StructureSection load='2pyf' size='340' side='right' caption='[[2pyf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='2pyf' size='340' side='right'caption='[[2pyf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2pyf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PYF FirstGlance]. <br>
<table><tr><td colspan='2'>[[2pyf]] is a 2 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=2PYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PYF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f53|2f53]], [[2f54|2f54]], [[2p5e|2p5e]], [[2p5w|2p5w]], [[2pye|2pye]], [[2bnr|2bnr]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pyf OCA], [http://pdbe.org/2pyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pyf RCSB], [http://www.ebi.ac.uk/pdbsum/2pyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pyf 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=2pyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pyf OCA], [https://pdbe.org/2pyf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pyf RCSB], [https://www.ebi.ac.uk/pdbsum/2pyf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pyf ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[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.
== Function ==
[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>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/py/2pyf_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/py/2pyf_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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==See Also==
==See Also==
*[[T-cell receptor|T-cell receptor]]
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Baston, E]]
[[Category: Large Structures]]
[[Category: Boulter, J M]]
[[Category: Baston E]]
[[Category: Dunn, S]]
[[Category: Boulter JM]]
[[Category: Gao, F]]
[[Category: Dunn S]]
[[Category: Jakobsen, B K]]
[[Category: Gao F]]
[[Category: Li, Y]]
[[Category: Jakobsen BK]]
[[Category: Molloy, P]]
[[Category: Li Y]]
[[Category: Moysey, R]]
[[Category: Molloy P]]
[[Category: Rizkallah, P J]]
[[Category: Moysey R]]
[[Category: Sami, M]]
[[Category: Rizkallah PJ]]
[[Category: Todorov, P]]
[[Category: Sami M]]
[[Category: Vuidepot, A]]
[[Category: Todorov P]]
[[Category: Cdr3]]
[[Category: Vuidepot A]]
[[Category: High affinity]]
[[Category: Immune system]]
[[Category: Mutant]]
[[Category: Ny-eso-1]]
[[Category: Phage display]]
[[Category: T-cell receptor]]

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