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| | <StructureSection load='6c68' size='340' side='right'caption='[[6c68]], [[Resolution|resolution]] 2.59Å' scene=''> | | <StructureSection load='6c68' size='340' side='right'caption='[[6c68]], [[Resolution|resolution]] 2.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6c68]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C68 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C68 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c68]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C68 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6c68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c68 OCA], [http://pdbe.org/6c68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c68 RCSB], [http://www.ebi.ac.uk/pdbsum/6c68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c68 ProSAT]</span></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]] 2.59Å</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=6c68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c68 OCA], [https://pdbe.org/6c68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c68 RCSB], [https://www.ebi.ac.uk/pdbsum/6c68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c68 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Arnon, T]] | + | [[Category: Arnon T]] |
| - | [[Category: Bhattacharya, A]] | + | [[Category: Bhattacharya A]] |
| - | [[Category: Chu, J]] | + | [[Category: Chu J]] |
| - | [[Category: Friedman, N]] | + | [[Category: Friedman N]] |
| - | [[Category: Ko, A]] | + | [[Category: Ko A]] |
| - | [[Category: Laethem, F Van]]
| + | [[Category: Love NC]] |
| - | [[Category: Love, N C]] | + | [[Category: Lu J]] |
| - | [[Category: Lu, J]] | + | [[Category: Radaev S]] |
| - | [[Category: Radaev, S]] | + | [[Category: Saba I]] |
| - | [[Category: Saba, I]] | + | [[Category: Shifrut E]] |
| - | [[Category: Shifrut, E]] | + | [[Category: Singer A]] |
| - | [[Category: Singer, A]] | + | [[Category: Sun PD]] |
| - | [[Category: Sun, P D]] | + | [[Category: Sun X]] |
| - | [[Category: Sun, X]] | + | [[Category: Tikhonova A]] |
| - | [[Category: Tikhonova, A]] | + | [[Category: Van Laethem F]] |
| - | [[Category: Weng, N]] | + | [[Category: Weng N]] |
| - | [[Category: Immune system]] | + | |
| - | [[Category: Mhc-independent t cell receptor]]
| + | |
| Structural highlights
Publication Abstract from PubMed
During normal T cell development in the thymus, alphabeta TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide-MHC ligands together with CD4/CD8 coreceptors. Conversely, in MHC and CD4/CD8 coreceptor-deficient mice, the thymus generates mature T cells expressing MHC-independent TCRs that recognize native conformational epitopes rather than linear antigenic-peptides presented by MHC. To date, no structural information of MHC-independent TCRs is available, and their structural recognition of non-MHC ligand remains unknown. To our knowledge in this study, we determined the first structures of two murine MHC-independent TCRs (A11 and B12A) that bind with high nanomolar affinities to mouse adhesion receptor CD155. Solution binding demonstrated the Valphabeta-domain is responsible for MHC-independent B12A recognition of its ligand. Analysis of A11 and B12A sequences against various MHC-restricted and -independent TCR sequence repertoires showed that individual V-genes of A11 and B12A did not exhibit preference against MHC-restriction. Likewise, CDR3 alone did not discriminate against MHC binding, suggesting VDJ recombination together with Valpha/Vbeta pairing determine their MHC-independent specificity for CD155. The structures of A11 and B12A TCR are nearly identical to those of MHC-restricted TCR, including the conformations of CDR1 and 2. Mutational analysis, together with negative-staining electron microscopy images, showed that the CDR regions of A11 and B12A recognized epitopes on D1 domain of CD155, a region also involved in CD155 binding to poliovirus and Tactile in human. Taken together, MHC-independent TCRs adopt canonical TCR structures to recognize native Ags, highlighting the importance of thymic selection in determining TCR ligand specificity.
Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.,Lu J, Van Laethem F, Saba I, Chu J, Tikhonova AN, Bhattacharya A, Singer A, Sun PD J Immunol. 2020 Jun 15;204(12):3351-3359. doi: 10.4049/jimmunol.1901084. Epub, 2020 Apr 22. PMID:32321756[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu J, Van Laethem F, Saba I, Chu J, Tikhonova AN, Bhattacharya A, Singer A, Sun PD. Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155. J Immunol. 2020 Jun 15;204(12):3351-3359. doi: 10.4049/jimmunol.1901084. Epub, 2020 Apr 22. PMID:32321756 doi:http://dx.doi.org/10.4049/jimmunol.1901084
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