4nqe: Difference between revisions
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==Crystal structure of TCR- | |||
<StructureSection load='4nqe' size='340' side='right' caption='[[4nqe]], [[Resolution|resolution]] 2.10Å' scene=''> | ==Crystal structure of TCR-MR1 ternary complex bound to 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil== | ||
<StructureSection load='4nqe' size='340' side='right'caption='[[4nqe]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nqe]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4nqe]] is a 8 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=4NQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NQE FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2L4:1-DEOXY-1-({2,6-DIOXO-5-[(E)-(2-OXOETHYLIDENE)AMINO]-1,2,3,6-TETRAHYDROPYRIMIDIN-4-YL}AMINO)-D-RIBITOL'>2L4</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2L4:1-DEOXY-1-({2,6-DIOXO-5-[(E)-(2-OXOETHYLIDENE)AMINO]-1,2,3,6-TETRAHYDROPYRIMIDIN-4-YL}AMINO)-D-RIBITOL'>2L4</scene></td></tr> | |||
<tr | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nqe OCA], [https://pdbe.org/4nqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nqe RCSB], [https://www.ebi.ac.uk/pdbsum/4nqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nqe ProSAT]</span></td></tr> | ||
</table> | |||
[ | |||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/TRBC1_HUMAN TRBC1_HUMAN] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 16: | ||
T-cell activation by transitory neo-antigens derived from distinct microbial pathways.,Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantragoon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Van Sinderen D, Mak JY, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J Nature. 2014 Apr 2. doi: 10.1038/nature13160. PMID:24695216<ref>PMID:24695216</ref> | T-cell activation by transitory neo-antigens derived from distinct microbial pathways.,Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantragoon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Van Sinderen D, Mak JY, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J Nature. 2014 Apr 2. doi: 10.1038/nature13160. PMID:24695216<ref>PMID:24695216</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4nqe" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[MHC 3D structures|MHC 3D structures]] | |||
*[[MHC I 3D structures|MHC I 3D structures]] | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Birkinshaw RW]] | ||
[[Category: | [[Category: Rossjohn J]] | ||
Latest revision as of 11:27, 9 October 2024
Crystal structure of TCR-MR1 ternary complex bound to 5-(2-oxoethylideneamino)-6-D-ribitylaminouracilCrystal structure of TCR-MR1 ternary complex bound to 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil
Structural highlights
FunctionPublication Abstract from PubMedT cells discriminate between foreign and host molecules by recognizing distinct microbial molecules, predominantly peptides and lipids. Riboflavin precursors found in many bacteria and yeast also selectively activate mucosal-associated invariant T (MAIT) cells, an abundant population of innate-like T cells in humans. However, the genesis of these small organic molecules and their mode of presentation to MAIT cells by the major histocompatibility complex (MHC)-related protein MR1 (ref. 8) are not well understood. Here we show that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-d-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis. Although 5-A-RU does not bind MR1 or activate MAIT cells directly, it does form potent MAIT-activating antigens via non-enzymatic reactions with small molecules, such as glyoxal and methylglyoxal, which are derived from other metabolic pathways. The MAIT antigens formed by the reactions between 5-A-RU and glyoxal/methylglyoxal were simple adducts, 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), respectively, which bound to MR1 as shown by crystal structures of MAIT TCR ternary complexes. Although 5-OP-RU and 5-OE-RU are unstable intermediates, they became trapped by MR1 as reversible covalent Schiff base complexes. Mass spectra supported the capture by MR1 of 5-OP-RU and 5-OE-RU from bacterial cultures that activate MAIT cells, but not from non-activating bacteria, indicating that these MAIT antigens are present in a range of microbes. Thus, MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells. These pyrimidine adducts are microbial signatures for MAIT-cell immunosurveillance. T-cell activation by transitory neo-antigens derived from distinct microbial pathways.,Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantragoon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Van Sinderen D, Mak JY, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J Nature. 2014 Apr 2. doi: 10.1038/nature13160. PMID:24695216[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References
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