Capturing a Flavivirus Pre-Fusion Intermediate
Figure 5
Model of the initial stages of the pH-triggered E rearrangement on the viral surface during flavivirus cell entry.
Domains DI, DII, and DIII of E are colored red, yellow, and blue, respectively. The partially alpha-helical stem region is shown in magenta and the transmembrane helices in grey. The fusion loop at the distal end of DII is indicated in green. Low endosomal pH weakens inter- and intramolecular E contacts and induces the outward extension of the whole stem region or its N-terminal portion including helix H1, followed by the dissociation of the E dimers. Further structural repositioning of the E monomers allows the interaction with the endosomal target membrane via the fusion loop. E16 was shown to inhibit the formation of fusion-active E trimers, most probably by interfering with the rearrangement of the E domains as a consequence of adding mass to DIII and sterically clashing with neighboring E and Fab molecules. However, E16 may also sterically prohibit the contact of E with the target membranes.