4F7C: Crystal Structure Of Bovine Cd1d With Bound C12-Di-Sulfatide

Citation:
Abstract
NKT cells play important roles in immune surveillance. They rapidly respond to pathogens by detecting microbial glycolipids when presented by the non-classical MHC I homolog CD1d. Previously, ruminants were considered to lack NKT cells due to the lack of a functional CD1D gene. However, recent data suggest that cattle express CD1d with unknown function. In an attempt to characterize the function of bovine CD1d, we assessed the lipid binding properties of recombinant Bos taurus CD1d (boCD1d) in vitro. BoCD1d is able to bind glycosphingolipids (GSLs) with fatty acid chain lengths of C(18), while GSLs with fatty acids of C(24) do not bind. Crystal structures of boCD1d bound to a short-chain C(12)-di-sulfatide antigen, as well as short-chain C(16)-alphaGalCer revealed that the A pocket of boCD1d is restricted in size compared to that of both mouse and human CD1d, explaining the inability of long chain GSL's to bind to boCD1d. Moreover, while di-sulfatide is presented similarly compared to the presentation of sulfatide by mouse CD1d, alphaGalCer is presented differently at the cell surface, due to an amino acid Asp151Asn substitution that results in loss of intimate contacts between the alphaGalCer headgroup and CD1d. The altered alphaGalCer presentation by boCD1d also explains its lack of cross-activation of mouse iNKT cells and raises the interesting question of the nature and function of bovine lipid-reactive T cells.
PDB ID: 4F7CDownload
MMDB ID: 105056
PDB Deposition Date: 2012/5/15
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.86  Å
Source Organism:
Similar Structures:
Biological Unit for 4F7C: dimeric; determined by author and by software (PISA)
Molecular Components in 4F7C
Label Count Molecule
Proteins (2 molecules)
1
Cd1d Antigen, D Polypeptide
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
Chemicals (3 molecules)
1
2
2
1
* Click molecule labels to explore molecular sequence information.

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