title: 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.
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.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Skiba
authors.forename: K A
authors.initials: KA
authors.lastname: Martemyanov
authors.forename: A
authors.initials: A
authors.lastname: Elfenbein
authors.forename: J A
authors.initials: JA
authors.lastname: Hopp
authors.forename: A
authors.initials: A
authors.lastname: Bohm
authors.forename: W F
authors.initials: WF
authors.lastname: Simonds
authors.forename: V Y
authors.initials: VY
authors.lastname: Arshavsky
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002384:Catalysis; D002417:Cattle; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D044387:GTP-Binding Protein beta Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D010786:Photoreceptor Cells / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020710:RGS Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D015293:Transducin / Q000378:metabolism
chemical_list: D044387:GTP-Binding Protein beta Subunits; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin