Fig. 7.

A schematic model highlighting the changes in the conformational flexibility of caspase-6 along its path to proteolytic maturation. Initial intramolecular self-cleavage of the procaspase-6 zymogen at Asp-193 in the intersubunit linker results in significant exposure of the linker, the 130s region, the 26–32 region, and the substrate-binding loop L1, whereas L2 and L4 are engaged in a stabilizing interaction. The subsequent intermolecular cleavage of the prodomain at Asp-23 results in the protection of the 26–32 region. The complete removal of the linker on intermolecular cleavage at the Asp-179 site results in more exposure of regions in the 130s and all of the substrate-binding loops L1–L4. Also, on substrate binding (red ellipsoids), the 130s and the substrate-binding loops L1–L4 become protected to engage the substrate in the active site cavity. The intensities of the red and blue colors represent the exposure or protection, respectively, relative to the conformational flexibility of the procaspase-6 zymogen.