Direct interaction of the mouse cytomegalovirus m152/gp40 immunoevasin with RAE-1 isoforms.

摘要: Cytomegaloviruses (CMVs) are ubiquitous species-specific viruses that establish acute, persistent, and latent infections. Both human mouse CMVs encode proteins inhibit the activation of natural killer (NK) cells by downregulating cellular ligands for NK cell activating receptor, NKG2D. The MCMV glycoprotein m152/gp40 downregulates surface expression RAE-1 in order to avoid control vivo. So far it is unclear if there a direct interaction between m152 RAE-1, so, interacts differentially with five identified isoforms, which expressed as two groups MCMV-susceptible or resistant strains. To address these questions, we purified extracellular domains m152, performed size exclusion chromatography binding assays well analytical ultracentrifugation isothermal titration calorimetry characterize interactions quantitatively. We further evaluated role full-length naturally glycosylated cotransfected HEK293T cells. Our results confirmed binds directly, relatively tightly (Kd < 5 μM), 1:1 stoichiometry. quantitatively different depending on particular corresponding susceptibility downregulation m152. A PLWY motif found RAE-1β, although contributing its affinity does not influence γ δ, suggesting other differences contribute RAE-1/m152 interaction. Molecular modeling isoforms suggests potential site