title: Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.
abstract: Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee KIRs with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by KIRs.
authors.affiliation: Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
authors.forename: Q R
authors.initials: QR
authors.lastname: Fan
authors.forename: E O
authors.initials: EO
authors.lastname: Long
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D019281:Dimerization; D019143:Evolution, Molecular; D015236:HLA-C Antigens / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007694:Killer Cells, Natural / Q000276:immunology*; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry*; D054342:Receptors, KIR2DL1; D013045:Species Specificity; D013499:Surface Properties
chemical_list: D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D008239:Lysine