Transducin activates cGMP phosphodiesterase by trapping inhibitory γ subunit freed reversibly from the catalytic subunit in solution

Activation of cGMP phosphodiesterase (PDE) by activated transducin alpha subunit (T alpha*) is a necessary step to generate a light response in vertebrate photoreceptors. PDE in rods is a heterotetramer composed of two catalytic subunits, PDE alpha and PDE beta, and two inhibitory PDE gamma subunits, each binding to PDE alpha or PDE beta. Activation of PDE is achieved by relief of the inhibitory constraint of PDE gamma on the catalytic subunit. In this activation mechanism, it is widely believed that T alpha* binds to PDE gamma still bound to the catalytic subunit, and removes or displaces PDE gamma from the catalytic subunit. However, recent structural analysis showed that the binding of T alpha*to PDE gamma still bound to PDE alpha or PDE beta seems to be difficult because the binding site of PDE gamma to PDE alpha or PDE beta overlaps with the binding site to T alpha*. In the present study, we propose a novel activation mechanism of PDE, the trapping mechanism, in which T alpha* activates PDE by trapping PDE gamma released reversibly and spontaneously from the catalytic subunit. This mechanism well explains PDE activation byT alpha* in solution. Our further analysis with this mechanism suggests that more effective PDE activation in disk membranes is highly dependent on the membrane environment.