Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain, which mediates a specific interaction with Gbeta5. The role of such interactions in RGS function is unclear. RGS proteins can accelerate the kinetics of coupling of G protein-coupled receptors to G-protein-gated inwardly rectifying K(+) (GIRK) channels. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK channels in Xenopus oocytes to evaluate the effect of Gbeta5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When Gbeta5 was co-expressed with either RGS7 or RGS9, the acceleration of GIRK channel kinetics was strongly increased over that produced by RGS7 or RGS9 alone. RGS function was not enhanced by co-expression of Gbeta1, and co-expression of Gbeta5 alone had no effect on GIRK channel kinetics. Gbeta5 did not modulate the function either of RGS4, an RGS protein that lacks a GGL domain, or of a functional RGS7 construct in which the GGL domain was omitted. Enhancement of RGS7 function by Gbeta5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.275.5.3397 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Geometric Graph Learning to Predict Changes in Binding Free Energy and Protein Thermodynamic Stability upon Mutation.
J Phys Chem Lett
December 2023
Department of Mathematics, University of Kentucky, Lexington, Kentucky 40506, United States.
Accurate prediction of binding free energy changes upon mutations is vital for optimizing drugs, designing proteins, understanding genetic diseases, and cost-effective virtual screening. While machine learning methods show promise in this domain, achieving accuracy and generalization across diverse data sets remains a challenge. This study introduces Geometric Graph Learning for Protein-Protein Interactions (GGL-PPI), a novel approach integrating geometric graph representation and machine learning to forecast mutation-induced binding free energy changes.
View Article and Find Full Text PDFThe Repeating, Modular Architecture of the HtrA Proteases.
Biomolecules
June 2022
Structural Biology Group, Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
A conserved, 26-residue sequence [AA(X)[A/G][G/L](X)GDV[I/L](X)[V/L]NGE(X)V(X)] and corresponding structure repeating module were identified within the HtrA protease family using a non-redundant set (N = 20) of publicly available structures. While the repeats themselves were far from sequence perfect, they had notable conservation to a statistically significant level. Three or more repetitions were identified within each protein despite being statistically expected to randomly occur only once per 1031 residues.
View Article and Find Full Text PDFProtein Profiling of RGS6, a Pleiotropic Gene Implicated in Numerous Neuropsychiatric Disorders, Reveals Multi-Isoformic Expression and a Novel Brain-Specific Isoform.
eNeuro
February 2022
Department of Neuroscience and Pharmacology, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
A metanalysis identified regulator of G-protein signaling 6 () as one of 23 loci with pleiotropic effects on four or more human psychiatric disorders. This finding is significant as it confirms/extends the findings of numerous other studies implicating RGS6 in CNS function and pathology. RGS6 is a highly conserved member of the RGS protein family whose cellular roles are likely affected by mRNA splicing and alternative domain inclusion/exclusion.
View Article and Find Full Text PDFPreclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor.
J Med Chem
July 2020
Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
Article Synopsis
- Tankyrases 1 and 2 are key targets in WNT/β-catenin and Hippo signaling pathways, and the researchers focused on optimizing inhibitors previously developed with a specific triazole structure.
- A systematic lead optimization process involved changing side groups on the inhibitor while keeping the main structure intact, leading to a new series of compounds with significantly improved target inhibition.
- The optimized compounds demonstrated better solubility, efficacy, and favorable absorption properties, making them potentially effective treatments for colon cancer.
Evaluation of differential qPE9-1/DEP1 protein domains in rice grain length and weight variation.
Rice (N Y)
January 2019
Jiangsu Key Laboratory of Crop Genetics and Physiology / Key Laboratory of Plant Functional Genomics of the Ministry of Education / Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, Agricultural College of Yangzhou University, Yangzhou, 225009, China.
Background: qPE9-1/DEP1, encoding a G protein γ subunit, has multiple effects on plant architecture, grain size, and yield in rice. The qPE9-1 protein contains an N-terminal G gamma-like (GGL) domain, a putative transmembrane domain, and a C-terminal cysteine-rich domain. However, the roles of each domain remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!