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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Direct interaction of the mouse cytomegalovirus m152/gp40 immunoevasin with RAE-1 isoforms
Biochemistry, Volume 49, No. 11, Year 2010
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Description
Cytomegaloviruses (CMVs) are ubiquitous species-specific viruses that establish acute, persistent, and latent infections. Both human and mouse CMVs encode proteins that inhibit the activation of natural killer (NK) cells by downregulating cellular ligands for the NK cell activating receptor, NK.G2D. The MCMV glycoprotein ml52/gp40 downregulates the surface expression of RAE-1 to prevent NK cell, control in vivo. So far, it is unclear if there is a direct interaction between m152 and RAE-1 and, if so, if m152 interacts differentially with the five identified RAE-1 isoforms, which are expressed as two groups in MCMVsusceptible or -resistant mouse strains. To address these questions, we expressed and purified the extracellular domains of RAE-1 and m 152 and performed, size exclusion chromatography binding assays as well as analytical ultracentrifugation and isothermal titration calorimetry to characterize these interactions quantitatively. We further evaluated the role of full-length and naturally glycosylated m152 and RAE-1 in cotransfected HEK293T cells. Our results confirmed, that m152 binds RAE-1 directly, relatively tightly (K d < 5μM), and with 1:1 stoichiometry. The binding is quantitatively different depending on particular RAE-1 isoforms, corresponding to the susceptibility to downregulation by m 152. A PLWY motif found in RAE-1β, although contributing to its affinity for ml 52, does not influence the affinity of RAE-1γ or RAE-1δ, suggesting that other differences contribute to the RAE-1-m152 interaction. Molecular modeling of the different RAE-1 isoforms suggests a potential site for the m152 interaction. © 2010 American Chemical Society.
Authors & Co-Authors
Zhi, Li
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Mans, Janet
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Pretoria
University of Pretoria
Paskow, Michael J.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Brown, Patrick H.
United States, Bethesda
National Institute of Biomedical Imaging and Bioengineering Nibib
Schuck, Peter
United States, Bethesda
National Institute of Biomedical Imaging and Bioengineering Nibib
Jonjic̈, Stipan
Croatia, Rijeka
Faculty of Medicine, University of Rijeka
Natarajan, Kannan
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Margulies, David H.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Statistics
Citations: 32
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1021/bi902130j
e-ISSN:
15204995