|Title||Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand.|
|Publication Type||Journal Article|
|Year of Publication||1999|
|Authors||Tormo, J, Natarajan, K, Margulies, DH, Mariuzza, RA|
|Date Published||1999 Dec 9|
|Keywords||Antigens, Ly, Crystallography, X-Ray, Escherichia coli, H-2 Antigens, Humans, Killer Cells, Natural, Lectins, C-Type, Macromolecular Substances, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Protein Folding, Receptors, Immunologic, Receptors, NK Cell Lectin-Like, Recombinant Proteins, Sequence Alignment, Signal Transduction|
Natural killer (NK) cell function is regulated by NK receptors that interact with MHC class I (MHC-I) molecules on target cells. The murine NK receptor Ly49A inhibits NK cell activity by interacting with H-2D(d) through its C-type-lectin-like NK receptor domain. Here we report the crystal structure of the complex between the Ly49A NK receptor domain and unglycosylated H-2D(d). The Ly49A dimer interacts extensively with two H-2D(d) molecules at distinct sites. At one interface, a single Ly49A subunit contacts one side of the MHC-I peptide-binding platform, presenting an open cavity towards the conserved glycosylation site on the H-2D(d) alpha2 domain. At a second, larger interface, the Ly49A dimer binds in a region overlapping the CD8-binding site. The smaller interface probably represents the interaction between Ly49A on the NK cell and MHC-I on the target cell, whereas the larger one suggests an interaction between Ly49A and MHC-I on the NK cell itself. Both Ly49A binding sites on MHC-I are spatially distinct from that of the T-cell receptor.