Figure 6. Model correlating disorder vs. order of the DHBc extension domain with phenotypes in bacteria and hepatoma cells.

Opposite charges in WT-DHBc and the double mutant E109R_R124E facilitate folding of the extension domain, in cells probably accelerated by chaperones, proline cis-trans-isomerases, and/or perhaps the envelope proteins. The shape of the folded extension domain is a schematic approximation to the structural data. Protonation of the E109 carboxylate at low pH ablates the salt-bridge, possibly creating a trigger for a conformational switch. In the absence of opposite charges at positions 109 and 124 (R124E, E109R) repulsion or lack of attraction (R124Q, not shown) hamper folding of the extension domain. This may expose eukaryotic instability determinants and cause the apparent capsid instability in hepatoma cells.