FIGURE 7.

Model to account for Ca²⁺ effects on MPEG-5 reactivity and trypsin cleavage of the C-terminal tail. A, the model shows a representation of the IP₃R based on the EM structure reported by da Fonseca et al. (32) in which the densities corresponding to the ligand binding (pink), regulatory (gray), and channel domains (blue) are as shown. A cross-sectional side view with just two subunits is shown for clarity. The C-terminal tail is shown as projecting perpendicularly from the membrane and running in a central channel formed by the ligand binding domain. The model draws attention to a small vestibule above the channel domain, which is proposed to enlarge as a result of a Ca²⁺-driven conformational change arising from the outward movement of ligand binding and regulatory domains. This results in increased accessibility of an endogenous cluster of cysteines located in the vestibule to MPEG-5. The opening of a crevice in the ligand binding domain also allows increased accessibility of trypsin to a cleavage site in the tail. For additional details, see text.