Crystal structure of the multifunctional Gbeta5-RGS9 complex.
Regulators of G-protein signaling (RGS) proteins enhance the intrinsic GTPase activity of G protein alpha (Galpha) subunits and are vital for proper signaling kinetics downstream of G protein-coupled receptors (GPCRs). R7 subfamily RGS proteins specifically and obligately dimerize with the atypical G protein beta5 (Gbeta5) subunit through an internal G protein gamma (Ggamma)-subunit-like (GGL) domain. Here we present the 1.95-A crystal structure of the Gbeta5-RGS9 complex, which is essential for normal visual and neuronal signal transduction. This structure reveals a canonical RGS domain that is functionally integrated within a molecular complex that is poised for integration of multiple steps during G-protein activation and deactivation.
Cheever
Matthew L
ML
Department of Pharmacology, University of North Carolina School of Medicine, Campus Box 7365, Chapel Hill, North Carolina 27599-7365, USA.
Snyder
Jason T
JT
Gershburg
Svetlana
S
Siderovski
David P
DP
Harden
T Kendall
TK
Sondek
John
J
D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D020710:RGS Proteins / Q000737:chemistry*
C490611:GNB5 protein, human; D044387:GTP-Binding Protein beta Subunits; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9