5u1r: Difference between revisions
New page: '''Unreleased structure''' The entry 5u1r is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Structure of human MR1-diclofenac in complex with human MAIT A-F7 TCR== | ||
<StructureSection load='5u1r' size='340' side='right'caption='[[5u1r]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5u1r]] 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=5U1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U1R FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DIF:2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC+ACID'>DIF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=5u1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u1r OCA], [https://pdbe.org/5u1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u1r RCSB], [https://www.ebi.ac.uk/pdbsum/5u1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u1r ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HMR1_HUMAN HMR1_HUMAN] Has antigen presentation function. Involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T-cells (MAIT). MAIT cells are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal. Expression and MAIT cell recognition seem to be ligand-dependent.<ref>PMID:12794138</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals. | |||
Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.,Keller AN, Eckle SB, Xu W, Liu L, Hughes VA, Mak JY, Meehan BS, Pediongco T, Birkinshaw RW, Chen Z, Wang H, D'Souza C, Kjer-Nielsen L, Gherardin NA, Godfrey DI, Kostenko L, Corbett AJ, Purcell AW, Fairlie DP, McCluskey J, Rossjohn J Nat Immunol. 2017 Feb 6. doi: 10.1038/ni.3679. PMID:28166217<ref>PMID:28166217</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5u1r" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Keller AN]] | |||
[[Category: Rossjohn J]] | |||
Latest revision as of 16:18, 4 October 2023
Structure of human MR1-diclofenac in complex with human MAIT A-F7 TCRStructure of human MR1-diclofenac in complex with human MAIT A-F7 TCR
Structural highlights
FunctionHMR1_HUMAN Has antigen presentation function. Involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T-cells (MAIT). MAIT cells are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal. Expression and MAIT cell recognition seem to be ligand-dependent.[1] Publication Abstract from PubMedThe major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals. Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.,Keller AN, Eckle SB, Xu W, Liu L, Hughes VA, Mak JY, Meehan BS, Pediongco T, Birkinshaw RW, Chen Z, Wang H, D'Souza C, Kjer-Nielsen L, Gherardin NA, Godfrey DI, Kostenko L, Corbett AJ, Purcell AW, Fairlie DP, McCluskey J, Rossjohn J Nat Immunol. 2017 Feb 6. doi: 10.1038/ni.3679. PMID:28166217[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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