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Structure of the viral immunoevasin m12 (Smith) bound to the natural killer cell receptor NKR-P1B (B6)
Structural highlights
FunctionKRBBB_MOUSE Receptor for CLEC2D/OCIL. Ligand-binding contributes to inhibition of cytotoxic natural killer (NK) cells. May mediate MHC class I-independent "missing-self" recognition of allografts, tumor cells and virus-infected cells.[1] [2] Publication Abstract from PubMedNatural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ligand for the inhibitory and activating NKR-P1 (NK1.1) receptors. This murine cytomegalovirus (MCMV)-encoded protein, m12, restrains NK cell effector function by directly engaging the inhibitory NKR-P1B receptor. However, m12 also interacts with the activating NKR-P1A/C receptors to counterbalance m12 decoy function. Structural analyses reveal that m12 sequesters a large NKR-P1 surface area via a "polar claw" mechanism. Polymorphisms in, and ablation of, the viral m12 protein and host NKR-P1B/C alleles impact NK cell responses in vivo. Thus, we identify the long-sought foreign ligand for this key immunoregulatory NKR family and reveal how it controls the evolutionary balance of immune recognition during host-pathogen interplay. A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family.,Aguilar OA, Berry R, Rahim MM, Reichel JJ, Popovic B, Tanaka M, Fu Z, Balaji GR, Lau TN, Tu MM, Kirkham CL, Mahmoud AB, Mesci A, Krmpotic A, Allan DS, Makrigiannis AP, Jonjic S, Rossjohn J, Carlyle JR Cell. 2017 Mar 23;169(1):58-71.e14. doi: 10.1016/j.cell.2017.03.002. PMID:28340350[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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