title: Thermodynamic analysis of degenerate recognition by the NKG2D immunoreceptor: not induced fit but rigid adaptation.
abstract: The homodimeric immunoreceptor NKG2D drives the activation of effector cells following engagement of diverse, conditionally expressed MHC class I-like protein ligands. NKG2D recognition is highly degenerate in that a single surface on receptor monomers binds pairs of distinct surfaces on each structurally divergent ligand, simultaneously accommodating multiple nonconservative ligand allelic or isoform substitutions. In contrast to TCR-pMHC and other NK receptor-ligand interactions, thermodynamic and kinetic analyses of four NKG2D-ligand pairs (MIC-A*001, MIC-B*005, ULBP1, and RAE-1beta) reported here show that the relative enthalpic and entropic terms, heat capacity, association rates, and activation energy barriers are comparable to typical, rigid protein-protein interactions. Rather than "induced-fit" binding, NKG2D degeneracy is achieved using distinct interaction mechanisms at each rigid interface.
authors.affiliation: The Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: McFarland
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
mesh_terms: D000818:Animals; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011485:Protein Binding / Q000276:immunology; D017510:Protein Folding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D013696:Temperature; D013816:Thermodynamics; D014443:Tyrosine / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014443:Tyrosine