PHOTORECEPTOR PHOSPHODIESTERASE - INTERACTION OF INHIBITORY GAMMA-SUBUNIT AND CYCLIC-GMP WITH SPECIFIC BINDING-SITES ON CATALYTIC SUBUNITS

The photoreceptor phosphodiesterase (PDE6) is the central effector enz yme in the phototransduction cascade of photoreceptor cells. It is the only known PDE isoform the activity of which is regulated by interact ion with a heterotrimeric G protein. The rod PDE6 holoenzyme is a tetr americ protein consisting of two large catalytic alpha and beta subuni ts and two small gamma subunits, which serve as potent inhibitors of P DE6. In dark-adapted photoreceptors, the gamma subunits maintain PDE6 activity at a low level. When exposed to light the visual pigment rhod opsin activates the retinal G protein, transducin, leading to release of the inhibitory action of the gamma subunits. In addition to the act ive sites where cGMP is hydrolyzed, the alpha and beta catalytic subun its have high-affinity, noncatalytic cGMP binding sites. These noncata lytic sites do not directly regulate cGMP catalysis at the active site , but rather can modulate the affinity with which the gamma subunits b ind to the catalytic subunits. This article describes a number of expe rimental approaches that have recently been developed for studying the interactions between catalytic and inhibitory subunits of PDE6, as we ll as the dynamics of cGMP binding to and dissociation from the PDE6 n oncatalytic sites. (C) 1998 Academic Press.