Nature Immunology
2, 443 - 451 (2001)
doi:10.1038/87757
Complex structure of the activating immunoreceptor NKG2D and its MHC class I−like ligand MICAPingwei Li1, Daniel L. Morris1, Benjamin E. Willcox2, Alexander Steinle3, 4, Thomas Spies3
& Roland K. Strong11
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA. 2
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. 3
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. 4
Present address: Interfakultäres Institut für Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
Correspondence should be addressed to Roland K. Strong rstrong@fhcrc.orgThe major histocompatibility complex (MHC) class I homolog, MICA, is a stress-inducible ligand for NKG2D, a C-type lectin−like activating immunoreceptor. The crystal structure of this ligand-receptor complex that we report here 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 on either the  1 or 2 domains of MICA. The binding interactions are large in area and highly complementary. The central section of the 2-domain helix, disordered in the structure of MICA alone, is ordered in the complex and forms part of the NKG2D interface. The extensive flexibility of the interdomain linker of MICA is shown by its altered conformation when crystallized alone or in complex with NKG2D.
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