ABSTRACT
RGS proteins regulate the duration of G protein signaling by increasing the rate of GTP hydrolysis on G protein alpha subunits. The complex of RGS9 with type 5 G protein beta subunit (G beta 5) is abundant in photoreceptors, where it stimulates the GTPase activity of transducin. An important functional feature of RGS9-G beta 5 is its ability to activate transducin GTPase much more efficiently after transducin binds to its effector, cGMP phosphodiesterase. Here we show that different domains of RGS9-G beta 5 make opposite contributions toward this selectivity. G beta 5 bound to the G protein gamma subunit-like domain of RGS9 acts to reduce RGS9 affinity for transducin, whereas other structures restore this affinity specifically for the transducin-phosphodiesterase complex. We suggest that this mechanism may serve as a general principle conferring specificity of RGS protein action.
Subject(s)
3',5'-Cyclic-GMP Phosphodiesterases/metabolism , GTP-Binding Protein beta Subunits , Heterotrimeric GTP-Binding Proteins/metabolism , Photoreceptor Cells/metabolism , RGS Proteins/metabolism , 3',5'-Cyclic-GMP Phosphodiesterases/physiology , Animals , Catalysis , Cattle , Cyclic Nucleotide Phosphodiesterases, Type 6 , Kinetics , Protein Structure, Tertiary , Substrate Specificity , Transducin/metabolismABSTRACT
A 67-year-old man with a 12-year history of trigeminal neuralgia experienced multiple fainting episodes preceded by right facial pain. One episode resulted in cardiac arrest with successful resuscitation. Pacemaker insertion prevented further episodes of syncope despite the occurrence of pain. The fainting episodes and cardiac arrest are believed to be unusual manifestations of trigeminal neuralgia.
