title: The crystal structure of human CD1d with and without alpha-galactosylceramide.
abstract: The glycolipid alpha-galactosylceramide binds with high affinity to CD1d and stimulates natural killer T cells. Here we report the crystal structure of human CD1d in complex with synthetic alpha-galactosylceramide at a resolution of 3.0 A. The structure shows a tightly fit lipid in the CD1d binding groove, with the sphingosine chain bound in the C' pocket and the longer acyl chain anchored in the A' pocket. We also present the CD1d structure without lipid, which has a more open conformation of the binding groove, suggesting a dual conformation of CD1d in which the 'open' conformation is more able to load lipids. These structures provide clues as to how CD1 molecules load glycolipids as well as data to guide the design of new therapeutic agents.
authors: Cancer Research UK Receptor Structure Research Group, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
authors: Michael
authors: M
authors: Koch
authors: Victoria S
authors: VS
authors: Stronge
authors: Dawn
authors: D
authors: Shepherd
authors: Stephan D
authors: SD
authors: Gadola
authors: Bini
authors: B
authors: Mathew
authors: Gerd
authors: G
authors: Ritter
authors: Alan R
authors: AR
authors: Fersht
authors: Gurdyal S
authors: GS
authors: Besra
authors: Richard R
authors: RR
authors: Schmidt
authors: E Yvonne
authors: EY
authors: Jones
authors: Vincenzo
authors: V
authors: Cerundolo
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry; D018949:Antigens, CD1 / Q000737:chemistry*; D055610:Antigens, CD1d; D018360:Crystallography, X-Ray; D005699:Galactosylceramides / Q000737:chemistry*; D006017:Glycolipids / Q000737:chemistry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013110:Sphingosine / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D006017:Glycolipids; D008055:Lipids; C493154:alpha-galactosylceramide; D013110:Sphingosine