2FIK

Structure of a microbial glycosphingolipid bound to mouse CD1d

Summary for 2FIK

• Entry DOI: 10.2210/pdb2fik/pdb
• Related: 1CD1 1Z5L 1ZHN 1ZT4 2AKR
• Descriptor: T-cell surface glycoprotein CD1d1, B(2)-microglobulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: nkt cells, cd1d, mhc-fold, immune system, bacterial antigen, tcr
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 46248.38

Authors

Wu, D.,Zajonc, D.M. (deposition date: 2005-12-29, release date: 2006-03-21, Last modification date: 2024-11-13)

Primary citation

Wu, D.,Zajonc, D.M.,Fujio, M.,Sullivan, B.A.,Kinjo, Y.,Kronenberg, M.,Wilson, I.A.,Wong, C.H.
Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d.
Proc.Natl.Acad.Sci.Usa, 103:3972-3977, 2006

PubMed Abstract: 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.

PubMed: 16537470
DOI: 10.1073/pnas.0600285103

Experimental method

X-RAY DIFFRACTION (1.8 Å)