title: Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition.
abstract: Adenoviruses (Ads) subvert MHC class I Ag presentation and impair host anti-Ad cellular activities. Specifically, the Ad-encoded E3-19K immunomodulatory protein targets MHC class I molecules for retention within the endoplasmic reticulum of infected cells. We report the x-ray crystal structure of the Ad type 4 (Ad4) E3-19K of species E bound to HLA-A2 at 2.64-Å resolution. Structural analysis shows that Ad4 E3-19K adopts a tertiary fold that is shared only with Ad2 E3-19K of species C. A comparative analysis of the Ad4 E3-19K/HLA-A2 structure with our x-ray structure of Ad2 E3-19K/HLA-A2 identifies species-specific features in HLA-A2 recognition. Our analysis also reveals common binding characteristics that explain the promiscuous, and yet high-affinity, association of E3-19K proteins with HLA-A and HLA-B molecules. We also provide structural insights into why E3-19K proteins do not associate with HLA-C molecules. Overall, our study provides new information about how E3-19K proteins selectively engage with MHC class I to abrogate Ag presentation and counteract activation of CD8(+) T cells. The significance of MHC class I Ag presentation for controlling viral infections, as well as the threats of viral infections in immunocompromised patients, underline our efforts to characterize viral immunoevasins, such as E3-19K.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612;
authors.forename: Lenong
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago, IL 60612; and Center for Biomolecular Sciences, College of Pharmacy, University of Illinois, Chicago, IL 60607.
authors.forename: Bernard D
authors.identifier: 0000-0002-9032-9699
authors.initials: BD
authors.lastname: Santarsiero
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612; mbouvier@uic.edu.
authors.forename: Marlene
authors.initials: M
authors.lastname: Bouvier
mesh_terms: D000256:Adenoviridae / Q000276:immunology* / Q000648:ultrastructure*; D017503:Adenovirus E3 Proteins / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology / Q000648:ultrastructure; D006801:Humans; D011487:Protein Conformation; D013045:Species Specificity
chemical_list: D017503:Adenovirus E3 Proteins; D015789:HLA-A2 Antigen