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Targeting of a natural killer cell receptor family by a viral immunoevasin

Berry, R., Ng, N., Saunders, P., Vivian, J., Lin, J., Deuss, F., Corbett, A., Forbes, C., Widjaja, J., Sullivan, L., McAlister, A., Perugini, M., Call, M., Scalzo, A., Degli-Esposti, M., Coudert, J., Beddoe, T., Brooks, A. and Rossjohn, Jamie 2013. Targeting of a natural killer cell receptor family by a viral immunoevasin. Nature Immunology 14 (7) , pp. 699-705. 10.1038/ni.2605

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Activating and inhibitory receptors on natural killer (NK) cells have a crucial role in innate immunity, although the basis of the engagement of activating NK cell receptors is unclear. The activating receptor Ly49H confers resistance to infection with murine cytomegalovirus by binding to the 'immunoevasin' m157. We found that m157 bound to the helical stalk of Ly49H, whereby two m157 monomers engaged the Ly49H dimer. The helical stalks of Ly49H lay centrally across the m157 platform, whereas its lectin domain was not required for recognition. Instead, m157 targeted an 'aromatic peg motif' present in stalks of both activating and inhibitory receptors of the Ly49 family, and substitution of this motif abrogated binding. Furthermore, ligation of m157 to Ly49H or Ly49C resulted in intracellular signaling. Accordingly, m157 has evolved to 'tackle the legs' of a family of NK cell receptors.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Amino Acid Motifs; Amino Acid Sequence; Animals; Crystallography, X-Ray; Female; Herpesviridae Infections; Histocompatibility Antigens Class I; Immunity, Innate; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Muromegalovirus; NK Cell Lectin-Like Receptor Subfamily A; Signal Transduction; Specific Pathogen-Free Organisms; Surface Plasmon Resonance
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of Acceptance: 2013
Last Modified: 04 Jun 2017 08:20

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