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| | ==Crystal structure of a human Valpha7.2/Vbeta13.3 MAIT TCR in complex with bovine MR1== | | ==Crystal structure of a human Valpha7.2/Vbeta13.3 MAIT TCR in complex with bovine MR1== |
| - | <StructureSection load='4l8s' size='340' side='right' caption='[[4l8s]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4l8s' size='340' side='right'caption='[[4l8s]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4l8s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L8S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4l8s]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L8S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.9Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KFP:N~6~-[(2-AMINO-4-OXO-3,4-DIHYDROPTERIDIN-6-YL)METHYL]-D-LYSINE'>KFP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KFP:N~6~-[(2-AMINO-4-OXO-3,4-DIHYDROPTERIDIN-6-YL)METHYL]-D-LYSINE'>KFP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4iiq|4iiq]], [[4l9l|4l9l]]</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=4l8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l8s OCA], [https://pdbe.org/4l8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l8s RCSB], [https://www.ebi.ac.uk/pdbsum/4l8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l8s ProSAT]</span></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=4l8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l8s OCA], [http://pdbe.org/4l8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4l8s RCSB], [http://www.ebi.ac.uk/pdbsum/4l8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4l8s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HMR1_BOVIN HMR1_BOVIN] Antigen-presenting molecule specialized in displaying microbial pyrimidine-based metabolites to alpha-beta T cell receptors (TCR) on innate-type mucosal-associated invariant T (MAIT) cells. In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (By similarity). Signature pyrimidine-based microbial antigens are generated via non-enzymatic condensation of metabolite intermediates of the riboflavin pathway with by-products arising from other metabolic pathways such as glycolysis. Typical potent antigenic metabolites are 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or methylglyoxal by-products, respectively (By similarity). May present microbial antigens to various MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin. Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (By similarity). During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora (By similarity). Acts as an immune sensor of cancer cell metabolome. May present a tumor-specific or -associated metabolite essential for cancer cell survival to a pan-cancer TCR on a non-MAIT CD8-positive T cell clone, triggering T cell-mediated killing of a wide range of cancer cell types (By similarity).[UniProtKB:Q8HWB0][UniProtKB:Q95460][https://www.uniprot.org/uniprot/B2MG_BOVIN B2MG_BOVIN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| - | *[[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: Bos taurus]] |
| - | [[Category: Adams, E J]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lopez-Sagaseta, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Antigen]] | + | [[Category: Adams EJ]] |
| - | [[Category: Antigen presentation]] | + | [[Category: Lopez-Sagaseta J]] |
| - | [[Category: Antigen recognition]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin domain]]
| + | |
| - | [[Category: Mhc-class i]]
| + | |
| Structural highlights
Function
HMR1_BOVIN Antigen-presenting molecule specialized in displaying microbial pyrimidine-based metabolites to alpha-beta T cell receptors (TCR) on innate-type mucosal-associated invariant T (MAIT) cells. In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (By similarity). Signature pyrimidine-based microbial antigens are generated via non-enzymatic condensation of metabolite intermediates of the riboflavin pathway with by-products arising from other metabolic pathways such as glycolysis. Typical potent antigenic metabolites are 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or methylglyoxal by-products, respectively (By similarity). May present microbial antigens to various MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin. Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (By similarity). During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora (By similarity). Acts as an immune sensor of cancer cell metabolome. May present a tumor-specific or -associated metabolite essential for cancer cell survival to a pan-cancer TCR on a non-MAIT CD8-positive T cell clone, triggering T cell-mediated killing of a wide range of cancer cell types (By similarity).[UniProtKB:Q8HWB0][UniProtKB:Q95460]B2MG_BOVIN Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Publication Abstract from PubMed
MR1-restricted mucosal-associated invariant T (MAIT) cells represent a subpopulation of alphabeta T cells with innate-like properties and limited TCR diversity. MAIT cells are of interest because of their reactivity against bacterial and yeast species, suggesting that they play a role in defense against pathogenic microbes. Despite the advances in understanding MAIT cell biology, the molecular and structural basis behind their ability to detect MR1-Ag complexes is unclear. In this study, we present our structural and biochemical characterization of MAIT TCR engagement of MR1 presenting an Escherichia coli-derived stimulatory ligand, rRL-6-CH2OH, previously found in Salmonella typhimurium. We show a clear enhancement of MAIT TCR binding to MR1 due to the presentation of this ligand. Our structure of a MAIT TCR/MR1/rRL-6-CH2OH complex shows an evolutionarily conserved binding orientation, with a clear role for both the CDR3alpha and CDR3beta loops in recognizing the rRL-6-CH2OH stimulatory ligand. We also present two additional xenoreactive MAIT TCR/MR1 complexes that recapitulate the docking orientation documented previously, despite having variation in the CDR2beta and CDR3beta loop sequences. Our data support a model by which MAIT TCRs engage MR1 in a conserved fashion, with their binding affinities modulated by the nature of the MR1-presented Ag or diversity introduced by alternate Vbeta usage or CDR3beta sequences.
MAIT Recognition of a Stimulatory Bacterial Antigen Bound to MR1.,Lopez-Sagaseta J, Dulberger CL, McFedries A, Cushman M, Saghatelian A, Adams EJ J Immunol. 2013 Nov 15;191(10):5268-77. doi: 10.4049/jimmunol.1301958. Epub 2013 , Oct 9. PMID:24108697[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lopez-Sagaseta J, Dulberger CL, McFedries A, Cushman M, Saghatelian A, Adams EJ. MAIT Recognition of a Stimulatory Bacterial Antigen Bound to MR1. J Immunol. 2013 Nov 15;191(10):5268-77. doi: 10.4049/jimmunol.1301958. Epub 2013 , Oct 9. PMID:24108697 doi:http://dx.doi.org/10.4049/jimmunol.1301958
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