Figure 8.

Model of allosteric communication within the regulatory tandem GAF domains. The GAFab structural model for the cGMP- and Pγ-bound state (Figure 6(a)) is shown with the major structural elements undergoing ligand-dependent conformational changes in the GAFa (red labels) and GAFb (orange labels). Pγ subunits are indicated by thick yellow and orange lines, while the catalytic domains are represented as light blue ovals based on the overall domain arrangement of rod PDE6 holoenzyme. Arrows indicate the proposed interactions that convey allosteric changes upon cGMP and/or Pγ binding, and gray spheres represent the sites of disease-causing mutations in human cone PDE6. See Discussion for details.