This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2fik
From Proteopedia
OCA (Talk | contribs)
(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...)
Next diff →
Revision as of 08:27, 21 November 2007
|
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
Page seeded by OCA on Wed Nov 21 10:34:29 2007
Categories: Mus musculus | Protein complex | Wu, D. | Zajonc, D.M. | GSL | NAG | PLM | Bacterial antigen | Cd1d | Immune system | Mhc-fold | Nkt cells | Tcr
