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

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

SUBMITTER: Asano T 

PROVIDER: S-EPMC6510727 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature