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| | ==Crystal structure of a human MAIT TCR in complex with bovine MR1== | | ==Crystal structure of a human MAIT TCR in complex with bovine MR1== |
| - | <StructureSection load='4iiq' size='340' side='right' caption='[[4iiq]], [[Resolution|resolution]] 2.86Å' scene=''> | + | <StructureSection load='4iiq' size='340' side='right'caption='[[4iiq]], [[Resolution|resolution]] 2.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iiq]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IIQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IIQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iiq]] 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=4IIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IIQ 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]] 2.86Å</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MR1, Bt.63045 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=4iiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iiq OCA], [https://pdbe.org/4iiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iiq RCSB], [https://www.ebi.ac.uk/pdbsum/4iiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iiq 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=4iiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iiq OCA], [http://pdbe.org/4iiq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iiq RCSB], [http://www.ebi.ac.uk/pdbsum/4iiq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iiq 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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| | </div> | | </div> |
| | <div class="pdbe-citations 4iiq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4iiq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Adams, E J]] | + | [[Category: Large Structures]] |
| - | [[Category: Lopez-Sagaseta, J]] | + | [[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
Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved alphabeta T-cell lineage that express a semi-invariant T-cell receptor (TCR) restricted to the MHC related-1 (MR1) protein. MAIT cells are dependent upon MR1 expression and exposure to microbes for their development and stimulation, yet these cells can exhibit microbial-independent stimulation when responding to MR1 from different species. We have used this microbial-independent, cross-species reactivity of MAIT cells to define the molecular basis of MAIT-TCR/MR1 engagement and present here a 2.85 A complex structure of a human MAIT-TCR bound to bovine MR1. The MR1 binding groove is similar in backbone structure to classical peptide-presenting MHC class I molecules (MHCp), yet is partially occluded by large aromatic residues that form cavities suitable for small ligand presentation. The docking of the MAIT-TCR on MR1 is perpendicular to the MR1 surface and straddles the MR1 alpha1 and alpha2 helices, similar to classical alphabeta TCR engagement of MHCp. However, the MAIT-TCR contacts are dominated by the alpha-chain, focused on the MR1 alpha2 helix. TCR beta-chain contacts are mostly through the variable CDR3beta loop that is positioned proximal to the CDR3alpha loop directly over the MR1 open groove. The elucidation of the MAIT TCR/MR1 complex structure explains how the semi-invariant MAIT-TCR engages the nonpolymorphic MR1 protein, and sheds light onto ligand discrimination by this cell type. Importantly, this structure also provides a critical link in our understanding of the evolution of alphabeta T-cell recognition of MHC and MHC-like ligands.
The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins.,Lopez-Sagaseta J, Dulberger CL, Crooks JE, Parks CD, Luoma AM, McFedries A, Van Rhijn I, Saghatelian A, Adams EJ Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1771-8. doi:, 10.1073/pnas.1222678110. Epub 2013 Apr 23. PMID:23613577[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lopez-Sagaseta J, Dulberger CL, Crooks JE, Parks CD, Luoma AM, McFedries A, Van Rhijn I, Saghatelian A, Adams EJ. The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins. Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1771-8. doi:, 10.1073/pnas.1222678110. Epub 2013 Apr 23. PMID:23613577 doi:10.1073/pnas.1222678110
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