2ial

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[[Image:2ial.png|left|200px]]
 
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{{STRUCTURE_2ial| PDB=2ial | SCENE= }}
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==Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR==
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<StructureSection load='2ial' size='340' side='right'caption='[[2ial]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2ial]] is a 4 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=2IAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IAL FirstGlance]. <br>
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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]] 1.92&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ial FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ial OCA], [https://pdbe.org/2ial PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ial RCSB], [https://www.ebi.ac.uk/pdbsum/2ial PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ial ProSAT]</span></td></tr>
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</table>
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== Disease ==
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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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== 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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ia/2ial_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ial ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.
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===Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR===
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Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.,Deng L, Langley RJ, Brown PH, Xu G, Teng L, Wang Q, Gonzales MI, Callender GG, Nishimura MI, Topalian SL, Mariuzza RA Nat Immunol. 2007 Apr;8(4):398-408. Epub 2007 Mar 4. PMID:17334368<ref>PMID:17334368</ref>
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{{ABSTRACT_PUBMED_17334368}}
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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 2ial" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[2ial]] is a 4 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=2IAL OCA].
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*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017334368</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Deng, L.]]
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[[Category: Large Structures]]
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[[Category: Langley, R J.]]
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[[Category: Deng L]]
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[[Category: Mariuzza, R A.]]
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[[Category: Langley RJ]]
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[[Category: Immune system]]
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[[Category: Mariuzza RA]]
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[[Category: Major histocompatibility complex]]
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[[Category: Melanoma]]
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[[Category: T cell receptor]]
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[[Category: T cell stimulation]]
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[[Category: Tumor antigen]]
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Current revision

Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

PDB ID 2ial

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