2fik

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spinqualitylabelsall models 2fik, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 NAG, GSL and PLM 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

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