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 enzyme in the phototransduction cascade of photoreceptor cells. It is the only known PDE isoform the activity of which is regulated by interaction with a heterotrimeric G protein. The rod PDE6 holoenzyme is a tetrameric protein consisting of two large catalytic alpha and beta subunits and two small gamma subunits, which serve as potent inhibitors of PDE6. In dark-adapted photoreceptors, the gamma subunits maintain PDE6 activity at a low level. When exposed to light the visual pigment rhodopsin activates the retinal G protein, transducin, leading to release of the inhibitory action of the gamma subunits. In addition to the active sites where cGMP is hydrolyzed, the alpha and beta catalytic subunits have high-affinity, noncatalytic cGMP binding sites. These noncatalytic sites do not directly regulate cGMP catalysis at the active site, but rather can modulate the affinity with which the gamma subunits bind to the catalytic subunits. This article describes a number of experimental approaches that have recently been developed for studying the interactions between catalytic and inhibitory subunits of PDE6, as well as the dynamics of cGMP binding to and dissociation from the PDE6 noncatalytic sites.
Artemyev
N O
NO
Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Arshavsky
V Y
VY
Cote
R H
RH
D000663:Amphibians; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002417:Cattle; D003432:Cross-Linking Reagents; D006152:Cyclic GMP / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000201:enzymology*; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D014357:Trypsin / Q000378:metabolism
D003432:Cross-Linking Reagents; D005136:Eye Proteins; D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D014357:Trypsin; D006152:Cyclic GMP