title: Crystal structure of the human natural killer cell activating receptor KIR2DS2 (CD158j).
abstract: Killer cell Ig-like receptors (KIRs) regulate the function of human natural killer and T cell subsets. A feature of the KIR locus is the clustering of homologous genes encoding for inhibitory and activating KIR. Inhibitory and activating KIR differ for ligand specificities and/or affinities. In particular, we show here with KIR tetramers that activating KIR2DS2 does not bind HLA-Cw3 molecules recognized by inhibitory KIR2DL2, despite 99% extracellular amino acid identity. We also report the 2.3-A structure of KIR2DS2, which reveals subtle displacements of two residues (Tyr45 and Gln71) involved in the interaction of KIR2DL2 with HLA-Cw3. These results show that KIR molecules cannot tolerate any variability in their three-dimensional structure without altering their MHC class I recognition capacities. Therefore, the mode of recognition used by KIR largely differs from the conformational changes that characterize T cell receptor or NKG2D interaction with their respective ligands.
authors.affiliation: Centre d'Immunologie INSERM-CNRS, de Marseille Luminy, Case 906, Parc Scientifique de Luminy, 13288 Marseille Cedex 09, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saulquin
authors.forename: Louis N
authors.initials: LN
authors.lastname: Gastinel
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
mesh_terms: D003460:Crystallization; D015236:HLA-C Antigens / Q000378:metabolism; D006801:Humans; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2
chemical_list: D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; C515077:KIR2DL2 protein, human; C433932:KIR2DS2 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2