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

Nature Structural & Molecular Biology volume 19, pages 1176–1181 (2012)Cite this article

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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 β2m. 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.

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Figure 1: The structure of Ad2 E3-19K–HLA-A2.
Figure 2: Interaction surface between Ad2 E3-19K and HLA-A2.
Figure 3: Electrostatic properties of interacting surfaces in Ad2 E3-19K and HLA-A2.
Figure 4: Conserved residues in Ad2 E3-19K.
Figure 5: Amino acid sequence alignment at the four interaction sites.

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Acknowledgements

This work was supported, in whole or in part, by the US National Institute of Allergy and Infectious Diseases grants R01 AI045070 and R56 AI102468 (to M.B.). We thank B. Santarsiero for help with X-ray data collection. Technical support by L. Qian for cell culture and protein purification is also acknowledged.

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  1. Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA

    Lenong Li, Yasameen Muzahim & Marlene Bouvier

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  1. Lenong Li
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Contributions

L.L., crystallographic and biochemical studies and manuscript preparation; Y.M., biochemical studies; M.B., project supervisor and manuscript preparation and principal manuscript author.

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Correspondence to Marlene Bouvier.

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Li, L., Muzahim, Y. & Bouvier, M. Crystal structure of adenovirus E3-19K bound to HLA-A2 reveals mechanism for immunomodulation. Nat Struct Mol Biol 19, 1176–1181 (2012). https://doi.org/10.1038/nsmb.2396

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