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| | <StructureSection load='4pjf' size='340' side='right'caption='[[4pjf]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='4pjf' size='340' side='right'caption='[[4pjf]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4pjf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PJF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4pjf]] 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=4PJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PJF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30W:N-(6-FORMYL-4-OXO-3,4-DIHYDROPTERIDIN-2-YL)ACETAMIDE'>30W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.45Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l4t|4l4t]], [[4nqc|4nqc]], [[4pj5|4pj5]], [[4pj7|4pj7]], [[4pj8|4pj8]], [[4pj9|4pj9]], [[4pja|4pja]], [[4pjb|4pjb]], [[4pjc|4pjc]], [[4pjd|4pjd]], [[4pje|4pje]], [[4pjg|4pjg]], [[4pjh|4pjh]], [[4pjx|4pjx]], [[4pji|4pji]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30W:N-(6-FORMYL-4-OXO-3,4-DIHYDROPTERIDIN-2-YL)ACETAMIDE'>30W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4pjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pjf OCA], [https://pdbe.org/4pjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pjf RCSB], [https://www.ebi.ac.uk/pdbsum/4pjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pjf 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=4pjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pjf OCA], [http://pdbe.org/4pjf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pjf RCSB], [http://www.ebi.ac.uk/pdbsum/4pjf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pjf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Birkinshaw, R W]] | + | [[Category: Birkinshaw RW]] |
| - | [[Category: Rossjohn, J]] | + | [[Category: Rossjohn J]] |
| - | [[Category: Ac-6-fp]]
| + | |
| - | [[Category: Immune complex]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Mr1]]
| + | |
| - | [[Category: Tcr]]
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| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) alpha-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR beta-chains. MAIT TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to structural alterations in MR1 that subsequently affected MAIT TCR recognition via conformational changes within the complementarity-determining region (CDR) 3beta loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3beta hypervariability impacted on MAIT TCR recognition by altering TCR flexibility and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition in an Ag-dependent manner, thereby modulating MAIT cell recognition.
A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells.,Eckle SB, Birkinshaw RW, Kostenko L, Corbett AJ, McWilliam HE, Reantragoon R, Chen Z, Gherardin NA, Beddoe T, Liu L, Patel O, Meehan B, Fairlie DP, Villadangos JA, Godfrey DI, Kjer-Nielsen L, McCluskey J, Rossjohn J J Exp Med. 2014 Jul 28;211(8):1585-600. doi: 10.1084/jem.20140484. Epub 2014 Jul , 21. PMID:25049336[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Miley MJ, Truscott SM, Yu YY, Gilfillan S, Fremont DH, Hansen TH, Lybarger L. Biochemical features of the MHC-related protein 1 consistent with an immunological function. J Immunol. 2003 Jun 15;170(12):6090-8. PMID:12794138
- ↑ Eckle SB, Birkinshaw RW, Kostenko L, Corbett AJ, McWilliam HE, Reantragoon R, Chen Z, Gherardin NA, Beddoe T, Liu L, Patel O, Meehan B, Fairlie DP, Villadangos JA, Godfrey DI, Kjer-Nielsen L, McCluskey J, Rossjohn J. A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells. J Exp Med. 2014 Jul 28;211(8):1585-600. doi: 10.1084/jem.20140484. Epub 2014 Jul , 21. PMID:25049336 doi:http://dx.doi.org/10.1084/jem.20140484
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