Journal article

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

R Berry, N Ng, PM Saunders, JP Vivian, J Lin, FA Deuss, AJ Corbett, CA Forbes, JM Widjaja, LC Sullivan, AD McAlister, MA Perugini, MJ Call, AA Scalzo, MA Degli-Esposti, JD Coudert, T Beddoe, AG Brooks, J Rossjohn

Nature Immunology | Published : 2013

Abstract

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 t..

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Grants

Funding Acknowledgements

We thank the staff of the crystallization facility of Monash University for assistance; A. Shahine, R. Koh, M. Peverelli and I. Larma for technical assistance; S. Lemieux (Institut Armand-Frappier) for the 4LO3311 hybridoma; and W. Yokoyama (Washington University) for BWZ HD12 and BWZ DAP12 cells and the 3D10 hybridoma. This research was undertaken on the MX2 beamline at the Australian Synchrotron, Victoria, Australia. Supported by the National Health and Medical Research Council of Australia (M.J.C., R. B., L. C. S., J.D.C. and J.R.), Australian Research Council (M. A. P., M.J.C. and J.P.V.) and Pfizer Australia (T.B.).