3vwk

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{{STRUCTURE_3vwk| PDB=3vwk | SCENE= }}
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==Ternary crystal structure of the human NKT TCR-CD1d-4'deoxy-alpha-galactosylceramide complex==
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===Ternary crystal structure of the human NKT TCR-CD1d-4'deoxy-alpha-galactosylceramide complex===
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<StructureSection load='3vwk' size='340' side='right' caption='[[3vwk]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
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{{ABSTRACT_PUBMED_22995911}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3vwk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VWK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VWK FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4GH:N-{(2S,3R)-1-[(4-DEOXY-ALPHA-D-XYLO-HEXOPYRANOSYL)OXY]-3-HYDROXYOCTADECAN-2-YL}HEXACOSANAMIDE'>4GH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2po6|2po6]], [[3huj|3huj]], [[3vwj|3vwj]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD1D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3vwk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vwk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vwk RCSB], [http://www.ebi.ac.uk/pdbsum/3vwk PDBsum]</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/CD1D_HUMAN CD1D_HUMAN]] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:17475845</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/CD1D_HUMAN CD1D_HUMAN]] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:17475845</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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Human and mouse type I NKT cells respond to a variety of CD1d-restricted glycolipid antigens (Ags), with their NKT cell antigen receptors (NKT TCRs) exhibiting reciprocal cross-species reactivity that is underpinned by a conserved NKT TCR-CD1d-Ag docking mode. Within this common docking footprint, the NKT TCR recognises, to varying degrees of affinity, a range of Ags. Presently it is unclear whether the human NKT TCRs will mirror the generalities underpinning the fine specificity of the mouse NKT TCR-CD1d-Ag interaction. Here, we assessed human NKT TCR recognition against altered glycolipid ligands of alpha-galactosylceramide (alpha-GalCer), and have determined the structures of a human NKT TCR in complex with CD1d-4',4''-deoxy-alpha-GalCer and CD1d-alpha-GalCer with a shorter, di-unsaturated acyl chain (C20:2). AGLs with acyl-chain modifications did not affect the affinity of the human NKT TCR-CD1d-Ag interaction. Surprisingly, human NKT TCR recognition is more tolerant to modifications at the 4'-OH position in comparison to the 3'-OH position of alpha-GalCer, which contrasts the fine specificity of the mouse NKT TCR-CD1d-Ag recognition (4'-OH &gt; 3'-OH). The fine specificity differences between human and mouse NKT TCRs was attributable to differing interactions between the respective complementarity determining region (CDR) 1alpha loops and the Ag. Accordingly, germline encoded fine-specificity differences underpin human and mouse type I NKT TCR interactions, which is an important considerations for therapeutic development and NKT cell physiology.
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==About this Structure==
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Human and mouse type I Natural Killer T-cell antigen receptors exhibit different fine specificities for CD1d-antigen.,Wun KS, Ross F, Patel O, Besra GS, Porcelli SA, Richardson SK, Keshipeddy S, Howell AR, Godfrey DI, Rossjohn J J Biol Chem. 2012 Sep 20. PMID:22995911<ref>PMID:22995911</ref>
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[[3vwk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VWK OCA].
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
==See Also==
==See Also==
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[T-cell receptor|T-cell receptor]]
*[[T-cell receptor|T-cell receptor]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:022995911</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Rossjohn, J.]]
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[[Category: Rossjohn, J]]
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[[Category: Wun, K S.]]
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[[Category: Wun, K S]]
[[Category: Alpha-galactosylceramide]]
[[Category: Alpha-galactosylceramide]]
[[Category: Cd1d]]
[[Category: Cd1d]]

Revision as of 07:19, 21 December 2014

Ternary crystal structure of the human NKT TCR-CD1d-4'deoxy-alpha-galactosylceramide complex

3vwk, resolution 2.94Å

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