Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand.
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.
Tormo
J
J
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville 20850, USA.
Natarajan
K
K
Margulies
D H
DH
Mariuzza
R A
RA
D000950:Antigens, Ly; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D006183:H-2 Antigens / Q000737:chemistry*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry*; D037181:Lectins, C-Type; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D011971:Receptors, Immunologic / Q000737:chemistry*; D055630:Receptors, NK Cell Lectin-Like; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D015398:Signal Transduction
D000950:Antigens, Ly; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D037181:Lectins, C-Type; D046911:Macromolecular Substances; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D011994:Recombinant Proteins