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| ==Crystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complex== | | ==Crystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complex== |
- | <StructureSection load='6mjq' size='340' side='right' caption='[[6mjq]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='6mjq' size='340' side='right'caption='[[6mjq]], [[Resolution|resolution]] 3.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6mjq]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=6MJQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MJQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mjq]] is a 8 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=6MJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MJQ FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JUD:N-{(2S,3S,4R)-3,4-dihydroxy-1-[(4-O-{[4-(trifluoromethyl)phenyl]methyl}-alpha-D-galactopyranosyl)oxy]octadecan-2-yl}hexacosanamide'>JUD</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B2M, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TRBC2, TCRBC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Cd1d1, mCG_3074 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JUD:~{N}-[(2~{S},3~{S},4~{R})-1-[(2~{S},3~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-3,4-bis(oxidanyl)-5-[[4-(trifluoromethyl)phenyl]methoxy]oxan-2-yl]oxy-3,4-bis(oxidanyl)octadecan-2-yl]hexacosanamide'>JUD</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6mjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mjq OCA], [http://pdbe.org/6mjq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mjq RCSB], [http://www.ebi.ac.uk/pdbsum/6mjq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mjq ProSAT]</span></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=6mjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mjq OCA], [https://pdbe.org/6mjq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mjq RCSB], [https://www.ebi.ac.uk/pdbsum/6mjq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mjq ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[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/A0A0B4J1J9_MOUSE A0A0B4J1J9_MOUSE] [https://www.uniprot.org/uniprot/K7N5M3_HUMAN K7N5M3_HUMAN] |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| </div> | | </div> |
| <div class="pdbe-citations 6mjq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6mjq" style="background-color:#fffaf0;"></div> |
| + | |
| + | ==See Also== |
| + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| + | *[[CD1|CD1]] |
| + | *[[T-cell receptor 3D structures|T-cell receptor 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
- | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
- | [[Category: Bitra, A]] | + | [[Category: Mus musculus]] |
- | [[Category: Janssens, J]] | + | [[Category: Bitra A]] |
- | [[Category: Zajonc, D M]] | + | [[Category: Janssens J]] |
- | [[Category: Glycolipid antigen presentation]] | + | [[Category: Zajonc DM]] |
- | [[Category: Ig-fold]]
| + | |
- | [[Category: Immune system]]
| + | |
- | [[Category: Immune system-inhibitor complex]]
| + | |
- | [[Category: Mhc-fold]]
| + | |
- | [[Category: T cell receptor]]
| + | |
| Structural highlights
6mjq is a 8 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Method: | X-ray diffraction, Resolution 3Å |
Ligands: | , , , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
A0A0B4J1J9_MOUSE K7N5M3_HUMAN
Publication Abstract from PubMed
Invariant natural killer T-cells (iNKT) are a glycolipid-responsive subset of T-lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, alpha-galactosylceramide (alpha-GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT-cells. Nonetheless, the potential of alpha-GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1- and Th2-cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4"-O-alkylated alpha-GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4"-OH group to ether moieties decreases the immunogenic potential in mice relative to alpha-GalCer. Yet, the benzyl-modified glycolipids are able to produce a distinct pro-inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the alpha2-helix of CD1d.
4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.,Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S. 4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies. ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652 doi:http://dx.doi.org/10.1002/cmdc.201800649
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