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Crystal structure of the murine NK cell–activating receptor NKG2D at 1.95 Å

Nature Immunology volume 2, pages 248–254 (2001)Cite this article

Abstract

NKG2D, a homodimeric lectin-like receptor, is a unique stimulatory molecule that is found on natural killer cells, T cells and activated macrophages. The natural ligands for murine NKG2D are distant major histocompatibility complex homologs, retinoic acid early transcript (Rae1) and H-60 minor histocompatibility antigen. The crystal structure of the extracellular region of murine NKG2D reveals close homology with other C-type lectin receptors such as CD94, Ly49A, rat MBP-A and CD69. However, the precise mode of dimeric assembly varies among these natural killer receptors, as well as their surface topography and electrostatic properties. The NKG2D structure provides the first structural insights into the role and ligand specificity of this stimulatory receptor in the innate and adaptive immune system.

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Figure 1: Anatomy of NKG2D and comparison with other C-type lectins.
Figure 2: Structure of the murine NKG2D homodimer.
Figure 3: NKG2D dimer interactions.
Figure 4: Comparison of disulfide bridges at the dimer interfaces of NKG2D, CD94 and Ly49A.
Figure 5: Sequence alignment of murine NKG2D with members of C-type lectin family.
Figure 6: Comparison of dimeric assembly and electrostatic surface potential of NKG2D, CD94 and Ly49A.
Figure 7: Potential interacting surfaces of murine and human NKG2D with ligands MICA and MICB.

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Acknowledgements

We thank S. Greasley, A. Heine, N. Larsen and X. Dai for data collection and processing; S. Greasley, A. Heine and J. Speir for helpful suggestions; A. Heine for invaluable advice with molecular replacement; R. Stanfield and J. Stevens for critical comments; R. Stanfield for help with computational calculations; M. Elsliger for computational assistance; and the staff of SSRL beamline 9-2. Supported by National Institutes of Health grants CA58896 and AI42266 (to I. A. W.); DK55037 and AI62267 (to L. T.); a Gerhard Hess research fellowship of the Deutsche Forschungsgemeinschaft (to D. H. B); a post-doctoral fellowship of the German Academic Exchange Service (to M. G. R.); and a National Science Foundation predoctoral fellowship (to D. W. W.).

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Authors and Affiliations

  1. Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Dennis W. Wolan, Markus G. Rudolph & Ian A. Wilson

  2. Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Luc Teyton

  3. Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Trogerstrasse 9, Munich, 81675, Germany

    Brigitte Villmow, Stefan Bauer & Dirk H. Busch

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Correspondence to Dirk H. Busch or Ian A. Wilson.

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Wolan, D., Teyton, L., Rudolph, M. et al. Crystal structure of the murine NK cell–activating receptor NKG2D at 1.95 Å. Nat Immunol 2, 248–254 (2001). https://doi.org/10.1038/85311

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