Crystal structure of adenovirus E3-19K protein bound to HLA-A2 reveals mechanism for immunomodulation

Abstract

Event Abstract Back to Event Crystal structure of adenovirus E3-19K protein bound to HLA-A2 reveals mechanism for immunomodulation Lenong Li1, Marlene Bouvier1* and Yasameen Muzahim1 1 University of Illinois at Chicago, College of Medicine, Microbiology and Immunology, United States The cell-surface presentation of viral antigens by MHC class I molecules is critical for eliminating host infected cells. In turn, viruses have evolved various strategies to interfere with antigen processing and presentation. The adenovirus (Ad) E3-19K protein binds to and retains MHC class I molecules in the endoplasmic reticulum (ER), thereby suppressing anti-Ad activities of CD8+ T-cells. E3-19K is a type I transmembrane glycoprotein that comprises a N-terminus ER-lumenal domain, a transmembrane domain, and a C-terminus cytosolic tail. The ER-lumenal domain of E3-19K associates with the ER-lumenal domain of MHC I, while the dilysine motif in the cytosolic tail of E3-19K provides the signal for localization of the E3-19K/MHC I complex in the ER. We will describe a novel rescue refolding strategy that allowed formation of the Ad serotype 2 (Ad2) E3-19K/HLA-A2 complex, from which we recently grew crystals diffracting 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 β2m. Ad2 E3-19K has a unique structure comprised of a large N-terminal domain, formed by two partially overlapping β-sheets arranged in a V-shape, 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 of different Ad species and MHC I of different HLA loci suggests a universal binding mode for all E3-19K proteins. Our structure offers explanations for the mechanism by which E3-19K modulates antiviral cellular immunity. Acknowledgements Supported by NIH grants R01 AI045070-12 and R56 AI102468-01. References Li, L., Muzahim, Y., and Bouvier, M. (2012) Crystal structure of adenovirus E3-19K bound to HLA-A2 reveals mechanism for immunomodulation. Nat. Struc. Molec. Biol. 19: 1176-1181. Keywords: MHC I, Antigen Presentation, adenovirus, viral immune evasion mechanisms, structural immunology Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Li L, Bouvier M and Muzahim Y (2013). Crystal structure of adenovirus E3-19K protein bound to HLA-A2 reveals mechanism for immunomodulation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00955 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Marlene Bouvier, University of Illinois at Chicago, College of Medicine, Microbiology and Immunology, Chicago, Illinois, 60612, United States, mbouvier@uic.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lenong Li Marlene Bouvier Yasameen Muzahim Google Lenong Li Marlene Bouvier Yasameen Muzahim Google Scholar Lenong Li Marlene Bouvier Yasameen Muzahim PubMed Lenong Li Marlene Bouvier Yasameen Muzahim Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.