3QUY: Structure Of The Mouse Cd1d-Bnnh-Gsl-1'-Inkt Tcr Complex

Citation:
Abstract
Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic alpha-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Th1 response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains. This induced fit is in contrast to another Th1-biasing glycolipid, alpha-C-GalCer, whose CD1d binding follows a conventional key-lock principle. These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. We speculate that glycolipids can be designed that induce a similar fit, thereby leading to superior and more sustained iNKT cell responses in vivo.
PDB ID: 3QUYDownload
MMDB ID: 91906
PDB Deposition Date: 2011/2/24
Updated in MMDB: 2011/07
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 3QUY: tetrameric; determined by author and by software (PISA)
Molecular Components in 3QUY
Label Count Molecule
Proteins (4 molecules)
1
Antigen-presenting Glycoprotein Cd1d1(Gene symbol: Cd1d1)
Molecule annotation
1
Beta-2 Microglobulin
Molecule annotation
1
Valpha14 (Mouse Variable Domain, Human Constant Domain)
Molecule annotation
1
Vbeta8.2 (Mouse Variable Domain, Human Constant Domain)
Molecule annotation
Chemicals (7 molecules)
1
4
2
1
3
1
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.