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== | ==Structure of the mouse CD1d-PyrC-alpha-GalCer-iNKT TCR complex== | ||
[[http://www.uniprot.org/uniprot/CD1D1_MOUSE CD1D1_MOUSE | <StructureSection load='4irs' size='340' side='right'caption='[[4irs]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4irs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IRS 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1LA:N-[(2S,3S,4R)-3,4-DIHYDROXY-1-{[6-O-(PYRIDIN-4-YLCARBAMOYL)-ALPHA-D-GALACTOPYRANOSYL]OXY}OCTADECAN-2-YL]HEXACOSANAMIDE'>1LA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4irs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4irs OCA], [https://pdbe.org/4irs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4irs RCSB], [https://www.ebi.ac.uk/pdbsum/4irs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4irs ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CD1D1_MOUSE CD1D1_MOUSE] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:11754812</ref> <ref>PMID:16314439</ref> <ref>PMID:16007091</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. Although it was previously thought that recognition of glycolipids such as alpha-galactosylceramide (alpha-GalCer) by the NKT cell TCR (NKTCR) obeys a key-lock principle, it is now clear this interaction is much more flexible. In this article, we report the structure-function analysis of a series of novel 6''-OH analogs of alpha-GalCer with more potent antitumor characteristics. Surprisingly, one of the novel carbamate analogs, alpha-GalCer-6''-(pyridin-4-yl)carbamate, formed novel interactions with the NKTCR. This interaction was associated with an extremely high level of Th1 polarization and superior antitumor responses. These data highlight the in vivo relevance of adding aromatic moieties to the 6''-OH position of the sugar and additionally show that judiciously chosen linkers are a promising strategy to generate strong Th1-polarizing glycolipids through increased binding either to CD1d or to NKTCR. | |||
Enhanced TCR Footprint by a Novel Glycolipid Increases NKT-Dependent Tumor Protection.,Aspeslagh S, Nemcovic M, Pauwels N, Venken K, Wang J, Van Calenbergh S, Zajonc DM, Elewaut D J Immunol. 2013 Aug 19. PMID:23960235<ref>PMID:23960235</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
< | </div> | ||
[[ | <div class="pdbe-citations 4irs" style="background-color:#fffaf0;"></div> | ||
[[ | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | ||
[[Category: | *[[CD1|CD1]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Nemcovic M]] | |||
[[Category: Zajonc DM]] | |||
Latest revision as of 13:59, 6 November 2024
Structure of the mouse CD1d-PyrC-alpha-GalCer-iNKT TCR complexStructure of the mouse CD1d-PyrC-alpha-GalCer-iNKT TCR complex
Structural highlights
FunctionCD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3] Publication Abstract from PubMedNKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. Although it was previously thought that recognition of glycolipids such as alpha-galactosylceramide (alpha-GalCer) by the NKT cell TCR (NKTCR) obeys a key-lock principle, it is now clear this interaction is much more flexible. In this article, we report the structure-function analysis of a series of novel 6-OH analogs of alpha-GalCer with more potent antitumor characteristics. Surprisingly, one of the novel carbamate analogs, alpha-GalCer-6-(pyridin-4-yl)carbamate, formed novel interactions with the NKTCR. This interaction was associated with an extremely high level of Th1 polarization and superior antitumor responses. These data highlight the in vivo relevance of adding aromatic moieties to the 6-OH position of the sugar and additionally show that judiciously chosen linkers are a promising strategy to generate strong Th1-polarizing glycolipids through increased binding either to CD1d or to NKTCR. Enhanced TCR Footprint by a Novel Glycolipid Increases NKT-Dependent Tumor Protection.,Aspeslagh S, Nemcovic M, Pauwels N, Venken K, Wang J, Van Calenbergh S, Zajonc DM, Elewaut D J Immunol. 2013 Aug 19. PMID:23960235[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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