Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands
|Title||Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||McFarland, B. J., Kortemme T., Yu S. F., Baker D., & Strong R. K.|
|Date Published||2003 Apr|
|Keywords||Amino Acids, Animals, Collaborative Publication, Crystallography, X-Ray, Genes, MHC Class I, HLA-A Antigens, Humans, Ligands, Mice, Models, Molecular, Mutagenesis, NK Cell Lectin-Like Receptor Subfamily K, Protein Structure, Tertiary, Receptors, Immunologic, Receptors, Natural Killer Cell|
Engagement of diverse protein ligands (MIC-A/B, ULBP, Rae-1, or H60) by NKG2D immunoreceptors mediates elimination of tumorigenic or virally infected cells by natural killer and T cells. Three previous NKG2D-ligand complex structures show the homodimeric receptor interacting with the monomeric ligands in similar 2:1 complexes, with an equivalent surface on each NKG2D monomer binding intimately to a total of six distinct ligand surfaces. Here, the crystal structure of free human NKG2D and in silico and in vitro alanine-scanning mutagenesis analyses of the complex interfaces indicate that NKG2D recognition degeneracy is not explained by a classical induced-fit mechanism. Rather, the divergent ligands appear to utilize different strategies to interact with structurally conserved elements of the consensus NKG2D binding site.