title: Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1γ reveals a paradigm for MHC/MHC interaction in immune evasion.
abstract: Natural killer (NK) cells are activated by engagement of the NKG2D receptor with ligands on target cells stressed by infection or tumorigenesis. Several human and rodent cytomegalovirus (CMV) immunoevasins down-regulate surface expression of NKG2D ligands. The mouse CMV MHC class I (MHC-I)-like m152/gp40 glycoprotein down-regulates retinoic acid early inducible-1 (RAE1) NKG2D ligands as well as host MHC-I. Here we describe the crystal structure of an m152/RAE1γ complex and confirm the intermolecular contacts by mutagenesis. m152 interacts in a pincer-like manner with two sites on the α1 and α2 helices of RAE1 reminiscent of the NKG2D interaction with RAE1. This structure of an MHC-I-like immunoevasin/MHC-I-like ligand complex explains the binding specificity of m152 for RAE1 and allows modeling of the interaction of m152 with classical MHC-I and of related viral immunoevasins.
authors.affiliation: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Kannan
authors.initials: K
authors.lastname: Natarajan
authors.forename: Maria Jamela R
authors.initials: MJ
authors.lastname: Revilleza
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Boyd
authors.forename: Li
authors.initials: L
authors.lastname: Zhi
authors.forename: Huaying
authors.initials: H
authors.lastname: Zhao
authors.forename: Howard
authors.initials: H
authors.lastname: Robinson
authors.forename: David H
authors.initials: DH
authors.lastname: Margulies
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D007107:Immune System; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008968:Molecular Conformation; D018146:Muromegalovirus / Q000378:metabolism*; D009154:Mutation; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000737:chemistry; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D020349:Surface Plasmon Resonance; D014764:Viral Proteins / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; D020033:Protein Isoforms; C490522:RAE1 protein, human; C490521:Rae1 protein, mouse; D014764:Viral Proteins; C104783:m152 protein, cytomegalovirus