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| | ==Structure of mouse CD1d in complex with PBS-25== | | ==Structure of mouse CD1d in complex with PBS-25== |
| - | <StructureSection load='3gmp' size='340' side='right' caption='[[3gmp]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='3gmp' size='340' side='right'caption='[[3gmp]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gmp]] 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=3GMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GMP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gmp]] is a 2 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=3GMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GMP 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=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=PBS:(2S,3S,4R)-N-OCTANOYL-1-[(ALPHA-D-GALACTOPYRANOSYL)OXY]-2-AMINO-OCTADECANE-3,4-DIOL'>PBS</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> | + | </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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PBS:(2S,3S,4R)-N-OCTANOYL-1-[(ALPHA-D-GALACTOPYRANOSYL)OXY]-2-AMINO-OCTADECANE-3,4-DIOL'>PBS</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></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]], [[3gmo|3gmo]], [[3gmq|3gmq]], [[3gml|3gml]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1z5l|1z5l]], [[2akr|2akr]], [[2fik|2fik]], [[2q7y|2q7y]], [[3gmr|3gmr]], [[3gmm|3gmm]], [[3gmn|3gmn]], [[3gmo|3gmo]], [[3gmq|3gmq]], [[3gml|3gml]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1d1, Cd1.1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m ([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=3gmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gmp OCA], [http://pdbe.org/3gmp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gmp RCSB], [http://www.ebi.ac.uk/pdbsum/3gmp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gmp 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=3gmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gmp OCA], [https://pdbe.org/3gmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gmp RCSB], [https://www.ebi.ac.uk/pdbsum/3gmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gmp 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. |
| | == 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/3gmp_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/3gmp_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: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Schiefner, A]] | | [[Category: Schiefner, A]] |
| Structural highlights
3gmp is a 2 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: | Cd1d1, Cd1.1 (LK3 transgenic mice), B2m (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.
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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