4lcw

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{{STRUCTURE_4lcw| PDB=4lcw | SCENE= }}
 
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===The structure of human MAIT TCR in complex with MR1-K43A-RL-6-Me-7OH===
 
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{{ABSTRACT_PUBMED_24101382}}
 
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==Disease==
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==The structure of human MAIT TCR in complex with MR1-K43A-RL-6-Me-7OH==
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<StructureSection load='4lcw' size='340' side='right' caption='[[4lcw]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4lcw]] 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=4LCW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LCW FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1VY:1-DEOXY-1-(7-HYDROXY-6-METHYL-2,4-DIOXO-3,4-DIHYDROPTERIDIN-8(2H)-YL)-D-RIBITOL'>1VY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l4v|4l4v]]</td></tr>
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<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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCR alpha ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCR beta ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=4lcw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lcw OCA], [http://pdbe.org/4lcw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lcw RCSB], [http://www.ebi.ac.uk/pdbsum/4lcw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lcw ProSAT]</span></td></tr>
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</table>
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== 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>
[[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>
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== Function ==
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==Function==
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[[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.
[[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) alpha-chain, TRAV1-2-TRAJ33, and are activated by vitamin B metabolites bound by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. Understanding MAIT cell biology has been restrained by the lack of reagents to specifically identify and characterize these cells. Furthermore, the use of surrogate markers may misrepresent the MAIT cell population. We show that modified human MR1 tetramers loaded with the potent MAIT cell ligand, reduced 6-hydroxymethyl-8-d-ribityllumazine (rRL-6-CH2OH), specifically detect all human MAIT cells. Tetramer(+) MAIT subsets were predominantly CD8(+) or CD4(-)CD8(-), although a small subset of CD4(+) MAIT cells was also detected. Notably, most human CD8(+) MAIT cells were CD8alpha(+)CD8beta(-/lo), implying predominant expression of CD8alphaalpha homodimers. Tetramer-sorted MAIT cells displayed a TH1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1-rRL-6-CH2OH tetramers detected CD4(+), CD4(-)CD8(-) and CD8(+) MAIT cells in Valpha19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-beta repertoire, and although the majority of human MAIT cells expressed TRAV1-2-TRAJ33, some expressed TRAJ12 or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow precise phenotypic characterization of human and mouse MAIT cells and revealed unanticipated TCR heterogeneity in this population.
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Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells.,Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Chen Z, Eckle SB, Uldrich AP, Birkinshaw RW, Patel O, Kostenko L, Meehan B, Kedzierska K, Liu L, Fairlie DP, Hansen TH, Godfrey DI, Rossjohn J, McCluskey J, Kjer-Nielsen L J Exp Med. 2013 Oct 21;210(11):2305-20. doi: 10.1084/jem.20130958. Epub 2013 Oct , 7. PMID:24101382<ref>PMID:24101382</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4lcw]] 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=4LCW OCA].
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</div>
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<div class="pdbe-citations 4lcw" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:024101382</ref><references group="xtra"/><references/>
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*[[Beta-2 microglobulin|Beta-2 microglobulin]]
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*[[T-cell receptor|T-cell receptor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Patel, O.]]
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[[Category: Patel, O]]
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[[Category: Rossjohn, J.]]
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[[Category: Rossjohn, J]]
[[Category: Mait t cell receptor]]
[[Category: Mait t cell receptor]]
[[Category: Membrane protein-immune system complex]]
[[Category: Membrane protein-immune system complex]]
[[Category: Mhc class i-related protein]]
[[Category: Mhc class i-related protein]]
[[Category: Vitamin b2 metabolite]]
[[Category: Vitamin b2 metabolite]]

Revision as of 08:41, 4 August 2016

The structure of human MAIT TCR in complex with MR1-K43A-RL-6-Me-7OH

4lcw, resolution 2.40Å

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