Journal article

Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition

Gautham R Balaji, Oscar A Aguilar, Miho Tanaka, Miguel A Shingu-Vazquez, Zhihui Fu, Benjamin S Gully, Lewis L Lanier, James R Carlyle, Jamie Rossjohn, Richard Berry

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018

Abstract

The interaction between natural killer (NK) cell inhibitory receptors and their cognate ligands constitutes a key mechanism by which healthy tissues are protected from NK cell-mediated lysis. However, self-ligand recognition remains poorly understood within the prototypical NKR-P1 receptor family. Here we report the structure of the inhibitory NKR-P1B receptor bound to its cognate host ligand, Clr-b. NKR-P1B and Clr-b interact via a head-to-head docking mode through an interface that includes a large array of polar interactions. NKR-P1B:Clr-b recognition is extremely sensitive to mutations at the heterodimeric interface, with most mutations severely impacting both Clr-b binding and NKR-P1B r..

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University of Melbourne Researchers

Grants

Awarded by Canadian Institutes of Health Research


Awarded by Australian Research Council Laureate Fellowship


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

The authors would like to thank the staff at the Monash Macromolecular Crystallization Facility and the Australian Synchrotron for their expert assistance. O.A.A. and L.L.L are supported by the Parker Institute for Cancer Immunotherapy. J.R.C. is supported by an operating grant from the Canadian Institutes of Health Research (106491). J.R. is a recipient of an Australian Research Council Laureate Fellowship (FL160100049). R.B. is a recipient of a National Health and Medical Research Council of Australia (NHMRC) Career Development Award (APP1109901).