3GMP

Structure of mouse CD1d in complex with PBS-25

Summary for 3GMP

• Entry DOI: 10.2210/pdb3gmp/pdb
• Related: 1Z5L 2AKR 2FIK 2Q7Y 3GML 3GMM 3GMN 3GMO 3GMQ 3GMR
• Descriptor: T-cell surface glycoprotein CD1d1, Beta-2 microglobulin, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: cd1, nkt cell, glycolipid, antigen presentation, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 47736.68

Authors

Schiefner, A.,Wilson, I.A. (deposition date: 2009-03-14, release date: 2009-11-10, Last modification date: 2023-09-06)

Primary citation

Schiefner, A.,Fujio, M.,Wu, D.,Wong, C.H.,Wilson, I.A.
Structural evaluation of potent NKT cell agonists: implications for design of novel stimulatory ligands.
J.Mol.Biol., 394:71-82, 2009

PubMed Abstract: Natural killer T (NKT) cells are a subset of T cells that are activated by CD1d-glycolipid complexes through a semi-invariant alphabeta T cell receptor (NKT TCR). Upon activation, NKT cells secrete regulatory cytokines that are implicated in T helper cell responses. alpha-Galactosylceramide (alpha-GalCer) is a potent NKT cell agonist when presented by CD1d. Phenyl ring substitutions of the alpha-GalCer fatty acid moiety were recently found to be superior in eliciting regulatory cytokines. Crystal structures of four new mouse CD1d-lipid complexes (five structures), a new PBS-25 complex, and CD1d with an endogenous ligand, at 1.6-1.9 A resolution, reveal that the alpha-GalCer phenyl analogues impart minor structural differences to the A'-pocket, while the sphingosine and galactose moieties, important for NKT TCR recognition, remain virtually unchanged. The observed differences in cytokine-release profiles appear to be associated with increased stability of the CD1d-glycolipid complexes rather than increased affinity for the NKT TCR. Furthermore, comparison of mouse CD1d-glycolipid complexes in different crystallographic space groups reveals considerable conformational variation, particularly above the F'-pocket, the primary site of interaction with the NKT TCR. We propose that modifications of the sphingosine moiety or other substitutions that decrease alpha-GalCer flexibility would stabilize the F'-pocket. Such compounds might then increase CD1d affinity for the NKT TCR and further enhance the stimulatory and regulatory properties of alpha-GalCer derivatives.

PubMed: 19732779
DOI: 10.1016/j.jmb.2009.08.061

Experimental method

X-RAY DIFFRACTION (1.7 Å)