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

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

Lenong Li, Yasameen Muzahim and Marlene Bouvier
Nature structural & molecular biology, Vol.19(11), pp.1176-1181
11/01/2012
DOI: 10.1038/nsmb.2396
PMCID: PMC3492506
PMID: 23042604

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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-angstrom resolution. Ad2 E3-19K binds to the N terminus of the HLA-A2 groove, contacting the alpha 1, alpha 2 and alpha 3 domains and beta(2)m. Ad2 E3-19K has a unique structure comprising a large N-terminal domain, formed by two partially overlapping beta-sheets arranged in a V shape, and a C-terminal alpha-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.
Biophysics Cell Biology Biochemistry & Molecular Biology Life Sciences & Biomedicine Science & Technology

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