Structure of acidic pH dengue virus showing the fusogenic glycoprotein trimers.

Zhang X, Sheng J, Austin SK, Hoornweg TE, Smit JM, Kuhn RJ, Diamond MS, Rossmann MG.

Citation

Zhang X, Sheng J, Austin SK, Hoornweg TE, Smit JM, Kuhn RJ, Diamond MS, Rossmann MG. (2015) Structure of acidic pH dengue virus showing the fusogenic glycoprotein trimers. Journal of Virology 89(1):743-750.

Abstract

The structure of a dengue virus has been captured during the formation of fusogenic trimers. This was accomplished by binding Fab fragments of the neutralizing antibody DV2-E104 to the virus at neutral pH and then decreasing the pH to 5.5. These trimers had an “open” conformation, which is distinct from the “closed” conformation of postfusion trimers. Only two of the three E proteins within each spike are bound by a Fab molecule at domain III. Steric hindrance around the icosahedral 3-fold axes prevents binding of a Fab to the third domain III of each E protein spike. Binding of the DV2-E104 Fab fragments prevents domain III from rotating by about 130Ã?° to the postfusion orientation and thus precludes the stem region from “zipping” together the three E proteins along the domain II boundaries into the “closed” postfusion conformation, thus inhibiting fusion.