title: Crystal structure of adenovirus E3-19K bound to HLA-A2 reveals mechanism for immunomodulation.
abstract: E3-19K binds to and retains MHC class I molecules in the endoplasmic reticulum, suppressing anti-adenovirus activities of T cells. We determined the structure of the adenovirus serotype 2 (Ad2, species C) E3-19K-HLA-A2 complex to 1.95-Å resolution. Ad2 E3-19K binds to the N terminus of the HLA-A2 groove, contacting the α1, α2 and α3 domains and β(2)m. Ad2 E3-19K has a unique structure comprising a large N-terminal domain, formed by two partially overlapping β-sheets arranged in a V shape, and a C-terminal α-helix and tail. The structure reveals determinants in E3-19K and HLA-A2 that are important for complex formation; conservation of some of these determinants in E3-19K proteins of different species and MHC I molecules of different loci suggests a universal binding mode for all E3-19K proteins. Our structure is important for understanding the immunomodulatory function of E3-19K.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois USA.
authors.forename: Lenong
authors.initials: L
authors.lastname: Li
authors.forename: Yasameen
authors.initials: Y
authors.lastname: Muzahim
authors.forename: Marlene
authors.initials: M
authors.lastname: Bouvier
mesh_terms: D017503:Adenovirus E3 Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D003001:Cloning, Molecular; D003461:Crystallography; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli; D015789:HLA-A2 Antigen / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017503:Adenovirus E3 Proteins; D015789:HLA-A2 Antigen