Thermodynamic analysis of degenerate recognition by the NKG2D immunoreceptor: not induced fit but rigid adaptation

Immunity. 2003 Dec;19(6):803-12. doi: 10.1016/s1074-7613(03)00320-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Histocompatibility Antigens / immunology
  • Humans
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Protein Binding / immunology
  • Protein Folding
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Immunologic / immunology*
  • Receptors, Natural Killer Cell
  • Temperature
  • Thermodynamics
  • Tyrosine / metabolism


  • Histocompatibility Antigens
  • KLRK1 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Tyrosine