RGS9-G beta 5 substrate selectivity in photoreceptors. Opposing effects of constituent domains yield high affinity of RGS interaction with the G protein-effector complex

• Published in: The Journal of biological chemistry 2001-10, Vol.276 (40), p.37365-37372
• Main Authors: Skiba, N P, Martemyanov, K A, Elfenbein, A, Hopp, J A, Bohm, A, Simonds, W F, Arshavsky, V Y
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - metabolism; 3',5'-Cyclic-GMP Phosphodiesterases - physiology; Animals; Catalysis; Cattle; Cyclic Nucleotide Phosphodiesterases, Type 6; GTP-Binding Protein beta Subunits; Heterotrimeric GTP-Binding Proteins - metabolism; Kinetics; phosphodiesterase; Photoreceptor Cells - metabolism; Protein Structure, Tertiary; RGS Proteins - metabolism; Substrate Specificity; Transducin - metabolism
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M106431200

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.