3GMO: Structure of mouse CD1d in complex with C8PhF

Citation:
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.
PDB ID: 3GMODownload
MMDB ID: 77982
PDB Deposition Date: 2009/3/14
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.6  Å
Source Organism:
Similar Structures:
Biological Unit for 3GMO: dimeric; determined by author and by software (PISA)
Molecular Components in 3GMO
Label Count Molecule
Proteins (2 molecules)
1
T-cell Surface Glycoprotein Cd1d1(Gene symbol: Cd1d1)
Molecule annotation
1
Beta-2 Microglobulin
Molecule annotation
Chemicals (18 molecules)
1
5
2
2
3
4
4
1
5
1
6
1
7
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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