Molecular insights into how the adenovirus E3-19K protein associates with MHC class I molecules (131.5)

Abstract

Abstract The immunomodulatory protein E3-19K from Adenoviruses (Ads) blocks cell surface expression of MHC class I by preventing their export from endoplasmic reticulum (ER), thus evading host's antiviral cellular immune responses. Currently, structural information on E3-19K and the biochemical properties of the E3-19K/class I complex is lacking. This knowledge will help not only to better understand host/virus interaction, but also to design effective antiviral therapies against Ad infections. Using a proteolytic approach, we showed that the recombinant, soluble E3-19K (residues 1-100) generated a large N- (residues 1-88) and small C- (residues 94-100) terminal fragments which encompass the majority of residues within the variable and conserved regions, respectively, of E3-19K. We showed that fragments corresponding to the variable and conserved regions do not remain associated together after proteolysis. Moreover, neither of these fragments associates with class I. These results strongly suggest that the ability of E3-19K to bind to class I molecules depends on a delicate structural interplay between the variable and conserved regions. We also identified residue 93 in E3-19K as critical for E3-19K association with class I molecules. Together, these results provide novel insights into the structure/function relationship of E3-19K and its effect on down regulation of class I molecules. Funded by NIH AI65943.