ArticleThe Journal of biological chemistry2010
A conserved protein interaction interface on the type 5 G protein beta subunit controls proteolytic stability and activity of R7 family regulator of G protein signaling proteins.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Identification of Gβ5 Interactome Associated with Neuronal Development in Neuro-2a Cells through miniTurbo Proximity Labeling.ACS omega · 2026Article
- RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease.Molecular pharmacology · 2020Review
- Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex.eLife · 2018Article
- Genome-Wide Screen for Genes Involved inG3 (Bethesda, Md.) · 2017Article
- Activity of theeLife · 2016Article
- GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition.Genome biology · 2016Article
- RGS6 as a Novel Therapeutic Target in CNS Diseases and Cancer.The AAPS journal · 2016Review
- Orphan Receptor GPR158 Is an Allosteric Modulator of RGS7 Catalytic Activity with an Essential Role in Dictating Its Expression and Localization in the Brain.The Journal of biological chemistry · 2015Article
- Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.Investigative ophthalmology & visual science · 2013Article
- Parasite neuropeptide biology: Seeding rational drug target selection?International journal for parasitology. Drugs and drug resistance · 2012Review
- GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes.The Journal of cell biology · 2012Article
- Gβ5-RGS complexes are gatekeepers of hyperactivity involved in control of multiple neurotransmitter systems.Psychopharmacology · 2012Article
- Membrane attachment is key to protecting transducin GTPase-activating complex from intracellular proteolysis in photoreceptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Type 5 G protein beta subunit (Gbeta5) controls the interaction of regulator of G protein signaling 9 (RGS9) with membrane anchors.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Regulators of G protein signaling (RGS) proteins of the R7 subfamily limit signaling by neurotransmitters in the brain and by light in the retina. They form obligate complexes with the Gβ5 protein that are subject to proteolysis to control their abundance and alter signaling. The mechanisms that regulate this proteolysis, however, remain unclear. We used genetic screens to find mutations in Gβ5 that selectively destabilize one of the R7 RGS proteins in Caenorhabditis elegans. These mutations cluster at the binding interface between Gβ5 and the N terminus of R7 RGS proteins. Equivalent mutations within mammalian Gβ5 allowed the interface to still bind the N-terminal DEP domain of R7 RGS proteins, and mutant Gβ5-R7 RGS complexes initially formed in cells but were then rapidly degraded by proteolysis. Molecular dynamics simulations suggest the mutations weaken the Gβ5-DEP interface, thus promoting dynamic opening of the complex to expose determinants of proteolysis known to exist on the DEP domain. We propose that conformational rearrangements at the Gβ5-DEP interface are key to controlling the stability of R7 RGS protein complexes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.