ArticleThe Journal of biological chemistry2017
Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Revealing GRK5 Activation Features by Interpretable Machine Learning and Molecular Dynamics Simulation.International journal of molecular sciences · 2026Article
- Explaining Conformational Diversity in Protein Families through Molecular Motions.Scientific data · 2024Article
- Multilevel superposition for deciphering the conformational variability of protein ensembles.Briefings in bioinformatics · 2024Article
- G protein-coupled receptor interactions with arrestins and GPCR kinases: The unresolved issue of signal bias.The Journal of biological chemistry · 2022Review
- Article
- The Open Question of How GPCRs Interact with GPCR Kinases (GRKs).Biomolecules · 2021Article
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- Stabilization of the Hinge Region of Human E-selectin Enhances Binding Affinity to Ligands Under Force.Cellular and molecular bioengineering · 2021Article
- Structure of a GRK5-Calmodulin Complex Reveals Molecular Mechanism of GRK Activation and Substrate Targeting.Molecular cell · 2021Article
- Characterization of a hyperphosphorylated variant of G protein-coupled receptor kinase 5 expressed in E. coli.Protein expression and purification · 2020Article
- Structure-Based Design of Selective, Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.ACS medicinal chemistry letters · 2019Article
- Computational study of paroxetine-like inhibitors reveals new molecular insight to inhibit GRK2 with selectivity over ROCK1.Scientific reports · 2019Article
- The dopamine D2 receptor can directly recruit and activate GRK2 without G protein activation.The Journal of biological chemistry · 2018Article
- Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors.Molecular pharmacology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR-mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well-understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family. Unlike most other AGC kinases, GRKs rely on their interaction with GPCRs for activation and not phosphorylation. Here, we used principal component analysis of available GRK and protein kinase A crystal structures to identify their dominant domain motions and to provide a framework that helps evaluate how close each GRK structure is to being a catalytically competent state. Our results indicated that disruption of an interface formed between the large lobe of the kinase domain and the regulator of G protein signaling homology domain (RHD) is highly correlated with establishment of the active conformation. By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both
Indexed as
Identifiers
What OpenQuestion holds
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.