|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the mouse CD1d-4ClPhC-alpha-GalCer-iNKT TCR complex== | | ==Structure of the mouse CD1d-4ClPhC-alpha-GalCer-iNKT TCR complex== |
| - | <StructureSection load='4irj' size='340' side='right' caption='[[4irj]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4irj' size='340' side='right'caption='[[4irj]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4irj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IRJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IRJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4irj]] 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=4IRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IRJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1L9:N-[(2S,3S,4R)-1-({6-O-[(4-CHLOROPHENYL)CARBAMOYL]-ALPHA-D-GALACTOPYRANOSYL}OXY)-3,4-DIHYDROXYOCTADECAN-2-YL]HEXACOSANAMIDE'>1L9</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1L9:N-[(2S,3S,4R)-1-({6-O-[(4-CHLOROPHENYL)CARBAMOYL]-ALPHA-D-GALACTOPYRANOSYL}OXY)-3,4-DIHYDROXYOCTADECAN-2-YL]HEXACOSANAMIDE'>1L9</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4irs|4irs]]</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=4irj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4irj OCA], [https://pdbe.org/4irj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4irj RCSB], [https://www.ebi.ac.uk/pdbsum/4irj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4irj ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1.1, CD1d, Cd1d1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m, beta-2-microglobulin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Valpha14 (mouse variable domain, human constant domain) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Vbeta8.2 (mouse variable domain, human constant domain) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4irj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4irj OCA], [http://pdbe.org/4irj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4irj RCSB], [http://www.ebi.ac.uk/pdbsum/4irj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4irj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] 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/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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 20: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | + | *[[CD1|CD1]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Nemcovic, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Zajonc, D M]] | + | [[Category: Mus musculus]] |
| - | [[Category: Antigen presentation]] | + | [[Category: Nemcovic M]] |
| - | [[Category: Glycolipid]] | + | [[Category: Zajonc DM]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Nkt cell]]
| + | |
| Structural highlights
Function
CD1D1_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 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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity. 2001 Dec;15(6):897-908. PMID:11754812
- ↑ Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439 doi:10.1084/jem.20051625
- ↑ Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005 Aug;6(8):810-8. Epub 2005 Jul 10. PMID:16007091 doi:10.1038/ni1224
- ↑ Aspeslagh S, Nemcovic M, Pauwels N, Venken K, Wang J, Van Calenbergh S, Zajonc DM, Elewaut D. Enhanced TCR Footprint by a Novel Glycolipid Increases NKT-Dependent Tumor Protection. J Immunol. 2013 Aug 19. PMID:23960235 doi:10.4049/jimmunol.1203134
|
