2fik
From Proteopedia
(New page: 200px<br /><applet load="2fik" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fik, resolution 1.80Å" /> '''Structure of a micro...) |
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| - | [[Image:2fik.gif|left|200px]]<br /><applet load="2fik" size=" | + | [[Image:2fik.gif|left|200px]]<br /><applet load="2fik" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fik, resolution 1.80Å" /> | caption="2fik, resolution 1.80Å" /> | ||
'''Structure of a microbial glycosphingolipid bound to mouse CD1d'''<br /> | '''Structure of a microbial glycosphingolipid bound to mouse CD1d'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Natural killer T (NKT) cells provide an innate-type immune response upon T | + | 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== | ==About this Structure== | ||
| - | 2FIK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG, GSL and PLM as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2FIK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=GSL:'>GSL</scene> and <scene name='pdbligand=PLM:'>PLM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FIK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Wu, D.]] | [[Category: Wu, D.]] | ||
| - | [[Category: Zajonc, D | + | [[Category: Zajonc, D M.]] |
[[Category: GSL]] | [[Category: GSL]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: tcr]] | [[Category: tcr]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:21:50 2008'' |
Revision as of 15:21, 21 February 2008
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Structure of a microbial glycosphingolipid bound to mouse CD1d
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
2FIK is a Protein complex structure of sequences from Mus musculus with , and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:21:50 2008
Categories: Mus musculus | Protein complex | Wu, D. | Zajonc, D M. | GSL | NAG | PLM | Bacterial antigen | Cd1d | Immune system | Mhc-fold | Nkt cells | Tcr
