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- | [[Image:2fik.gif|left|200px]] | |
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- | <!-- | + | ==Structure of a microbial glycosphingolipid bound to mouse CD1d== |
- | The line below this paragraph, containing "STRUCTURE_2fik", creates the "Structure Box" on the page.
| + | <StructureSection load='2fik' size='340' side='right'caption='[[2fik]], [[Resolution|resolution]] 1.80Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2fik]] 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=2FIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FIK FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSL:(2S,3R)-3-HYDROXY-2-(TETRADECANOYLAMINO)OCTADECYL+ALPHA-D-GALACTOPYRANOSIDURONIC+ACID'>GSL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> |
- | {{STRUCTURE_2fik| PDB=2fik | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fik OCA], [https://pdbe.org/2fik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fik RCSB], [https://www.ebi.ac.uk/pdbsum/2fik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fik ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [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 == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fi/2fik_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fik ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Natural killer T (NKT) cells provide an innate-type immune response upon T cell receptor interaction with CD1d-presented antigens. We demonstrate through equilibrium tetramer binding and antigen presentation assays with Valpha14i-positive NKT cell hybridomas that the Sphingomonas glycolipid alpha-galacturonosyl ceramide (GalA-GSL) is a NKT cell agonist that is significantly weaker than alpha-galactosylceramide (alpha-GalCer), the most potent known NKT agonist. For GalA-GSL, a shorter fatty acyl chain, an absence of the 4-OH on the sphingosine tail and a 6'-COOH group on the galactose moiety account for its observed antigenic potency. We further determined the crystal structure of mCD1d in complex with GalA-GSL at 1.8-A resolution. The overall binding mode of GalA-GSL to mCD1d is similar to that of the short-chain alpha-GalCer ligand PBS-25, but its sphinganine chain is more deeply inserted into the F' pocket due to alternate hydrogen-bonding interactions between the sphinganine 3-OH with Asp-80. Subsequently, a slight lateral shift (>1 A) of the galacturonosyl head group is noted at the CD1 surface compared with the galactose of alpha-GalCer. Because the relatively short C(14) fatty acid of GalA-GSL does not fully occupy the A' pocket, a spacer lipid is found that stabilizes this pocket. The lipid spacer was identified by GC/MS as a mixture of saturated and monounsaturated palmitic acid (C(16)). Comparison of available crystal structures of alpha-anomeric glycosphingolipids now sheds light on the structural basis of their differential antigenic potency and has led to the design and synthesis of NKT cell agonists with enhanced cell-based stimulatory activities compared with alpha-GalCer. |
| | | |
- | '''Structure of a microbial glycosphingolipid bound to mouse CD1d'''
| + | Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d.,Wu D, Zajonc DM, Fujio M, Sullivan BA, Kinjo Y, Kronenberg M, Wilson IA, Wong CH Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):3972-7. Epub 2006 Mar 6. PMID:16537470<ref>PMID:16537470</ref> |
- | | + | |
- | | + | |
- | ==Overview==
| + | |
- | Natural killer T (NKT) cells provide an innate-type immune response upon T cell receptor interaction with CD1d-presented antigens. We demonstrate through equilibrium tetramer binding and antigen presentation assays with Valpha14i-positive NKT cell hybridomas that the Sphingomonas glycolipid alpha-galacturonosyl ceramide (GalA-GSL) is a NKT cell agonist that is significantly weaker than alpha-galactosylceramide (alpha-GalCer), the most potent known NKT agonist. For GalA-GSL, a shorter fatty acyl chain, an absence of the 4-OH on the sphingosine tail and a 6'-COOH group on the galactose moiety account for its observed antigenic potency. We further determined the crystal structure of mCD1d in complex with GalA-GSL at 1.8-A resolution. The overall binding mode of GalA-GSL to mCD1d is similar to that of the short-chain alpha-GalCer ligand PBS-25, but its sphinganine chain is more deeply inserted into the F' pocket due to alternate hydrogen-bonding interactions between the sphinganine 3-OH with Asp-80. Subsequently, a slight lateral shift (>1 A) of the galacturonosyl head group is noted at the CD1 surface compared with the galactose of alpha-GalCer. Because the relatively short C(14) fatty acid of GalA-GSL does not fully occupy the A' pocket, a spacer lipid is found that stabilizes this pocket. The lipid spacer was identified by GC/MS as a mixture of saturated and monounsaturated palmitic acid (C(16)). Comparison of available crystal structures of alpha-anomeric glycosphingolipids now sheds light on the structural basis of their differential antigenic potency and has led to the design and synthesis of NKT cell agonists with enhanced cell-based stimulatory activities compared with alpha-GalCer.
| + | |
| | | |
- | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
- | 2FIK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FIK OCA].
| + | </div> |
| + | <div class="pdbe-citations 2fik" style="background-color:#fffaf0;"></div> |
| | | |
- | ==Reference== | + | ==See Also== |
- | Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d., Wu D, Zajonc DM, Fujio M, Sullivan BA, Kinjo Y, Kronenberg M, Wilson IA, Wong CH, Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):3972-7. Epub 2006 Mar 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16537470 16537470]
| + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| + | *[[CD1|CD1]] |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| + | [[Category: Large Structures]] |
| [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
- | [[Category: Protein complex]]
| + | [[Category: Wu D]] |
- | [[Category: Wu, D.]] | + | [[Category: Zajonc DM]] |
- | [[Category: Zajonc, D M.]] | + | |
- | [[Category: Bacterial antigen]]
| + | |
- | [[Category: Cd1d]]
| + | |
- | [[Category: Immune system]]
| + | |
- | [[Category: Mhc-fold]]
| + | |
- | [[Category: Nkt cell]]
| + | |
- | [[Category: Tcr]]
| + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:56:24 2008''
| + | |
| 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]
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 provide an innate-type immune response upon T cell receptor interaction with CD1d-presented antigens. We demonstrate through equilibrium tetramer binding and antigen presentation assays with Valpha14i-positive NKT cell hybridomas that the Sphingomonas glycolipid alpha-galacturonosyl ceramide (GalA-GSL) is a NKT cell agonist that is significantly weaker than alpha-galactosylceramide (alpha-GalCer), the most potent known NKT agonist. For GalA-GSL, a shorter fatty acyl chain, an absence of the 4-OH on the sphingosine tail and a 6'-COOH group on the galactose moiety account for its observed antigenic potency. We further determined the crystal structure of mCD1d in complex with GalA-GSL at 1.8-A resolution. The overall binding mode of GalA-GSL to mCD1d is similar to that of the short-chain alpha-GalCer ligand PBS-25, but its sphinganine chain is more deeply inserted into the F' pocket due to alternate hydrogen-bonding interactions between the sphinganine 3-OH with Asp-80. Subsequently, a slight lateral shift (>1 A) of the galacturonosyl head group is noted at the CD1 surface compared with the galactose of alpha-GalCer. Because the relatively short C(14) fatty acid of GalA-GSL does not fully occupy the A' pocket, a spacer lipid is found that stabilizes this pocket. The lipid spacer was identified by GC/MS as a mixture of saturated and monounsaturated palmitic acid (C(16)). Comparison of available crystal structures of alpha-anomeric glycosphingolipids now sheds light on the structural basis of their differential antigenic potency and has led to the design and synthesis of NKT cell agonists with enhanced cell-based stimulatory activities compared with alpha-GalCer.
Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d.,Wu D, Zajonc DM, Fujio M, Sullivan BA, Kinjo Y, Kronenberg M, Wilson IA, Wong CH Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):3972-7. Epub 2006 Mar 6. PMID:16537470[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
- ↑ Wu D, Zajonc DM, Fujio M, Sullivan BA, Kinjo Y, Kronenberg M, Wilson IA, Wong CH. Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):3972-7. Epub 2006 Mar 6. PMID:16537470
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