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Complex structure of the activating immunoreceptor NKG2D and its MHC class I–like ligand MICA

Nature Immunology volume 2, pages 443–451 (2001)Cite this article

Abstract

The 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 α1 or α2 domains of MICA. The binding interactions are large in area and highly complementary. The central section of the α2-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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Figure 1: The structure of the NKG2D-MICA complex.
Figure 2: Comparisons of NKG2D with other NKDs and C-type lectins.
Figure 3: The structure of MICA in the complex.
Figure 4: Details of the binding sites.
Figure 5: Affinity and kinetics measurements of the NKG2D–MICA interaction by SPR.

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Acknowledgements

We thank L. Hung, G. McDermott and T. Earnest (Advanced Light Source, Lawrence Berkeley National Laboratory) for assistance with data collection. Supported by National Institutes of Health grants AI42200 (to R. K. S.), CA18221 and AI30581 (to T. S.).

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Author notes

  1. Alexander Steinle

    Present address: Interfakultäres Institut für Zellbiologie, Abteilung Immunologie, Auf der Morgenstelle 15, D-72076, Tübingen, Germany

Authors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA

    Pingwei Li, Daniel L. Morris & Roland K. Strong

  2. Division of Biology, California Institute of Technology, Pasadena, 91125, CA, USA

    Benjamin E. Willcox

  3. Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA

    Alexander Steinle & Thomas Spies

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Correspondence to Roland K. Strong.

Additional information

Note added in proof: The structure of human NKG2D in the complex recapitulated all the salient features of the recently reported structure of murine NKG2D43.

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Li, P., Morris, D., Willcox, B. et al. Complex structure of the activating immunoreceptor NKG2D and its MHC class I–like ligand MICA. Nat Immunol 2, 443–451 (2001). https://doi.org/10.1038/87757

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