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| | ==Structure of mouse CD1d in complex with C8PhF== | | ==Structure of mouse CD1d in complex with C8PhF== |
| - | <StructureSection load='3gmo' size='340' side='right' caption='[[3gmo]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3gmo' size='340' side='right'caption='[[3gmo]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gmo]] is a 2 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=3GMO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GMO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gmo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GMO 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=C8F:8-(4-FLUOROPHENYL)-N-{(1S,2S,3R)-1-[(ALPHA-D-GALACTOPYRANOSYLOXY)METHYL]-2,3-DIHYDROXYHEPTADECYL}OCTANAMIDE'>C8F</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1z5l|1z5l]], [[2akr|2akr]], [[2fik|2fik]], [[2q7y|2q7y]], [[3gmr|3gmr]], [[3gmm|3gmm]], [[3gmn|3gmn]], [[3gmp|3gmp]], [[3gmq|3gmq]], [[3gml|3gml]]</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=C8F:8-(4-FLUOROPHENYL)-N-{(1S,2S,3R)-1-[(ALPHA-D-GALACTOPYRANOSYLOXY)METHYL]-2,3-DIHYDROXYHEPTADECYL}OCTANAMIDE'>C8F</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1d1, Cd1.1 ([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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gmo OCA], [https://pdbe.org/3gmo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gmo RCSB], [https://www.ebi.ac.uk/pdbsum/3gmo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gmo ProSAT]</span></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=3gmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gmo OCA], [http://pdbe.org/3gmo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gmo RCSB], [http://www.ebi.ac.uk/pdbsum/3gmo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gmo 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/3gmo_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/3gmo_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| | + | *[[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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Schiefner, A]] | + | [[Category: Mus musculus]] |
| - | [[Category: Wilson, I A]] | + | [[Category: Schiefner A]] |
| - | [[Category: Antigen presentation]] | + | [[Category: Wilson IA]] |
| - | [[Category: Cd1]]
| + | |
| - | [[Category: Glycolipid]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Nkt cell]]
| + | |
| Structural highlights
3gmo is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.6Å |
| Ligands: | , , , , , , |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Natural killer T (NKT) cells are a subset of T cells that are activated by CD1d-glycolipid complexes through a semi-invariant alphabeta T cell receptor (NKT TCR). Upon activation, NKT cells secrete regulatory cytokines that are implicated in T helper cell responses. alpha-Galactosylceramide (alpha-GalCer) is a potent NKT cell agonist when presented by CD1d. Phenyl ring substitutions of the alpha-GalCer fatty acid moiety were recently found to be superior in eliciting regulatory cytokines. Crystal structures of four new mouse CD1d-lipid complexes (five structures), a new PBS-25 complex, and CD1d with an endogenous ligand, at 1.6-1.9 A resolution, reveal that the alpha-GalCer phenyl analogues impart minor structural differences to the A'-pocket, while the sphingosine and galactose moieties, important for NKT TCR recognition, remain virtually unchanged. The observed differences in cytokine-release profiles appear to be associated with increased stability of the CD1d-glycolipid complexes rather than increased affinity for the NKT TCR. Furthermore, comparison of mouse CD1d-glycolipid complexes in different crystallographic space groups reveals considerable conformational variation, particularly above the F'-pocket, the primary site of interaction with the NKT TCR. We propose that modifications of the sphingosine moiety or other substitutions that decrease alpha-GalCer flexibility would stabilize the F'-pocket. Such compounds might then increase CD1d affinity for the NKT TCR and further enhance the stimulatory and regulatory properties of alpha-GalCer derivatives.
Structural evaluation of potent NKT cell agonists: implications for design of novel stimulatory ligands.,Schiefner A, Fujio M, Wu D, Wong CH, Wilson IA J Mol Biol. 2009 Nov 20;394(1):71-82. Epub 2009 Sep 2. PMID:19732779[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
- ↑ Schiefner A, Fujio M, Wu D, Wong CH, Wilson IA. Structural evaluation of potent NKT cell agonists: implications for design of novel stimulatory ligands. J Mol Biol. 2009 Nov 20;394(1):71-82. Epub 2009 Sep 2. PMID:19732779 doi:10.1016/j.jmb.2009.08.061
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