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Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition

Lenong Li, Bernard D. Santarsiero and Marlene Bouvier
J Immunol July 6, 2016, 1600541; DOI: https://doi.org/10.4049/jimmunol.1600541
Lenong Li
*Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612;
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Bernard D. Santarsiero
†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
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Marlene Bouvier
*Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612;
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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.

Footnotes

  • This work was supported in whole or in part by National Institute of Allergy and Infectious Diseases Grants R01AI108546 and R03AI114611 (to M.B.) and National Center for Complementary and Alternative Medicine Grant 1U41AT008706 (to B.D.S.).

  • The atomic coordinates and structure factors presented in this article have been submitted to the Protein Data Bank (http://www.rcsb.org/pdb/home/home.do) under accession number 5IRO.

  • The online version of this article contains supplemental material.

  • Received March 29, 2016.
  • Accepted June 2, 2016.
  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 206 (3)
The Journal of Immunology
Vol. 206, Issue 3
1 Feb 2021
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Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition
Lenong Li, Bernard D. Santarsiero, Marlene Bouvier
The Journal of Immunology July 6, 2016, 1600541; DOI: 10.4049/jimmunol.1600541

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Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition
Lenong Li, Bernard D. Santarsiero, Marlene Bouvier
The Journal of Immunology July 6, 2016, 1600541; DOI: 10.4049/jimmunol.1600541
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Print ISSN 0022-1767        Online ISSN 1550-6606