title: Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands.
abstract: 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.
authors.affiliation: The Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: McFarland
authors.forename: Tanja
authors.initials: T
authors.lastname: Kortemme
authors.forename: Shuyuarn F
authors.initials: SF
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D016296:Mutagenesis; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell
chemical_list: D000596:Amino Acids; D015234:HLA-A Antigens; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell