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| | ==Structure of the mouse CD1d-BnNH-GSL-1'-iNKT TCR complex== | | ==Structure of the mouse CD1d-BnNH-GSL-1'-iNKT TCR complex== |
| - | <StructureSection load='3quy' size='340' side='right' caption='[[3quy]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='3quy' size='340' side='right'caption='[[3quy]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3quy]] 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=3QUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QUY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3quy]] is a 4 chain structure with sequence from [https://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=3QUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QUY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QUY:(2S,3R,4S,5R,6S)-6-[(2S,3S,4R)-2-(HEXACOSANOYLAMINO)-3,4-DIHYDROXY-OCTADECOXY]-3,4,5-TRIHYDROXY-N-(PHENYLMETHYL)OXANE-2-CARBOXAMIDE'>QUY</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QUY:(2S,3R,4S,5R,6S)-6-[(2S,3S,4R)-2-(HEXACOSANOYLAMINO)-3,4-DIHYDROXY-OCTADECOXY]-3,4,5-TRIHYDROXY-N-(PHENYLMETHYL)OXANE-2-CARBOXAMIDE'>QUY</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qux|3qux]], [[3quz|3quz]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qux|3qux]], [[3quz|3quz]]</div></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, mCG_11606, RP23-34E24.5-001 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1.1, CD1d, Cd1d1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m, beta-2-microglobulin, mCG_11606, RP23-34E24.5-001 ([https://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=3quy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3quy OCA], [http://pdbe.org/3quy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3quy RCSB], [http://www.ebi.ac.uk/pdbsum/3quy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3quy 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=3quy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3quy OCA], [https://pdbe.org/3quy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3quy RCSB], [https://www.ebi.ac.uk/pdbsum/3quy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3quy 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> [[https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | *[[CD1|CD1]] | | *[[CD1|CD1]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Girardi, E]] | | [[Category: Girardi, E]] |
| Structural highlights
3quy is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | |
| Gene: | Cd1.1, CD1d, Cd1d1 (LK3 transgenic mice), B2m, beta-2-microglobulin, mCG_11606, RP23-34E24.5-001 (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Publication Abstract from PubMed
Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic alpha-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Th1 response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, alpha-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo.
Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.,Aspeslagh S, Li Y, Yu ED, Pauwels N, Trappeniers M, Girardi E, Decruy T, Van Beneden K, Venken K, Drennan M, Leybaert L, Wang J, Franck RW, Van Calenbergh S, Zajonc DM, Elewaut D EMBO J. 2011 Jun 1;30(11):2294-305. Epub 2011 May 6. PMID:21552205[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, Li Y, Yu ED, Pauwels N, Trappeniers M, Girardi E, Decruy T, Van Beneden K, Venken K, Drennan M, Leybaert L, Wang J, Franck RW, Van Calenbergh S, Zajonc DM, Elewaut D. Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis. EMBO J. 2011 Jun 1;30(11):2294-305. Epub 2011 May 6. PMID:21552205 doi:10.1038/emboj.2011.145
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