6n9g | pdb_00006n9g
Crystal Structure of RGS7-Gbeta5 dimer
Structural highlights
Function[RGS7_BOVIN] Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. The RGS7/GNB5 dimer enhances GNAO1 GTPase activity. May play a role in synaptic vesicle exocytosis. Modulates the activity of potassium channels that are activated by GNAO1 in response to muscarinic acetylcholine receptor M2/CHRM2 signaling.[UniProtKB:P49802] [GNB5_MOUSE] Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha subunits, thereby promoting their inactivation (Probable). Increases RGS9 GTPase-activating protein (GAP) activity, hence contributes to the deactivation of G protein signaling initiated by D(2) dopamine receptors (By similarity). May play an important role in neuronal signaling, including in the parasympathetic, but not sympathetic, control of heart rate (By similarity).[UniProtKB:A1L271][UniProtKB:O14775] Publication Abstract from PubMedSignaling by the G-protein-coupled receptors (GPCRs) plays fundamental role in a vast number of essential physiological functions. Precise control of GPCR signaling requires action of regulators of G protein signaling (RGS) proteins that deactivate heterotrimeric G proteins. RGS proteins are elaborately regulated and comprise multiple domains and subunits, yet structural organization of these assemblies is poorly understood. Here, we report a crystal structure and dynamics analyses of the multisubunit complex of RGS7, a major regulator of neuronal signaling with key roles in controlling a number of drug target GPCRs and links to neuropsychiatric disease, metabolism, and cancer. The crystal structure in combination with molecular dynamics and mass spectrometry analyses reveals unique organizational features of the complex and long-range conformational changes imposed by its constituent subunits during allosteric modulation. Notably, several intermolecular interfaces in the complex work in synergy to provide coordinated modulation of this key GPCR regulator. Structural organization of a major neuronal G protein regulator, the RGS7-Gbeta5-R7BP complex.,Patil DN, Rangarajan ES, Novick SJ, Pascal BD, Kojetin DJ, Griffin PR, Izard T, Martemyanov KA Elife. 2018 Dec 12;7. pii: 42150. doi: 10.7554/eLife.42150. PMID:30540250[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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