5IRO

Crystal structure of a complex between the Human adenovirus type 4 E3-19K protein and MHC class molecule HLA-A2/TAX

Summary for 5IRO

• Entry DOI: 10.2210/pdb5iro/pdb
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, TAX protein, Beta-2-microglobulin, ... (5 entities in total)
• Functional Keywords: ad4 e3-19k-hla-a2 complex, immune evasion function, mhc class i molecule, immune system-transcription complex, immune system/transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 24
• Total formula weight: 343187.72

Authors

Li, L.,Bouvier, M. (deposition date: 2016-03-14, release date: 2016-08-24, Last modification date: 2024-11-13)

Primary citation

Li, L.,Santarsiero, B.D.,Bouvier, M.
Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition.
J Immunol., 197:1399-1407, 2016

PubMed 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.

PubMed: 27385781
DOI: 10.4049/jimmunol.1600541

Experimental method

X-RAY DIFFRACTION (2.64 Å)