Complex structure of the activating immunoreceptor NKG2D and its MHC classI-like ligand MICA

The major histocompatibility complex (MHC) class I homolog, MICA, is a stre ss-inducible ligand for NKG2D, a C-type lectin-like activating immunorecept or,The crystal structure of this ligand-receptor complex that we report her e reveals an NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to that seen in T cell receptor-MHC class I protein complexes . Similar surfaces on each NKG2D monomer interact with different surfaces o n either the alpha1 or alpha2 domains of MICA.The binding interactions are large in area and highly complementary.The central section of the alpha2-do main helix, disordered in the structure of MICA alone, is ordered in the co mplex and forms part of the NKG2D interface.The extensive flexibility of th e interdomain linker of MICA is shown by its altered conformation when crys tallized alone or in complex with NKG2D.