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Biosensors for monitoring G protein-coupled receptors (GPCRs), the most drugged class of proteins in

October 2022 Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Simulations and Quantum Chemical Calculations "Allosteric modulators are called promising candidates in G

Most acquired genes are transmembrane proteins and cytokines, such as viral G protein-coupled receptors

October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias Cardiac contractility, essential to maintaining proper cardiac output and circulation, is regulated by G Previously, the absence of regulator of G protein signaling (RGS) 2 and 5, separately, was shown to cause G protein dysregulation, contributing to modest blood pressure elevation and exaggerated cardiac hypertrophic Whether RGS2 and 5 redundantly control G protein signaling to maintain cardiovascular homeostasis is

August 2022 GPCRs steer G i and G s selectivity via TM5-TM6 switches as revealed by structures of serotonin Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G The structural basis for G protein subtype selectivity by these GPCRs remains elusive. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures.

October 2022 "Biased G protein-coupled receptor (GPCR) ligands, which preferentially activate G protein behavior, reduced fertility, and memory impairment, which are potentially associated with impaired G In contrast to Gpr3-deficient mice, G protein-biased GPR3 mice do not display elevated anxiety levels in the area and compaction of amyloid plaques in the preclinical AppNL-G-F AD mouse model. hypertrophy, which suggest a protective glial response that may limit amyloid plaque development in G

Integration and Spatial Organization of Signaling by G Protein-Coupled Receptor Homo- and Heterodimer The G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, with nearly 800

G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor In vitro and in vivo data suggest that GHSR1a heterodimerises with multiple G protein-coupled receptors

October 2022 "Visual phototransduction is the most extensively studied G protein-coupled receptor (GPCR

Regulator G protein Signaling (RGS) proteins are critical components of the intracellular signaling pathways that mediate the effects of G protein-coupled receptors (GPCRs). core that catalyzes the hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate of the G also contain a range of other structural motifs that are critical for their function, including the G Hepler, Cellular regulation of RGS proteins: modulators and integrators of G protein signaling.

October 2022 "G protein-coupled receptors (GPCRs) are of considerable interest due to their importance relevance in the cardiovascular system of the three most important GPCR signaling effectors: heterotrimeric G

September 2022 "Metabotropic γ-aminobutyric acid receptor (GABABR), a class C G protein-coupled receptor Cryo-electron microscopy studies revealed a drastic conformational change upon activation and a unique G

October 2022 "Heterotrimeric G proteins couple activated G protein-coupled receptors (GPCR) to intracellular

Historically, ligands for GPCRs have been identified before their receptor counterparts. With the cloning revolution, several unidentified receptors have been found and were labelled as “orphan” for their endogenous ligands. Orphan GPCRs have been shown to play key roles in various physiological functions, such as sensory perception, reproduction, development, growth, metabolism, and are also linked to major diseases, such as neuroinflammatory, metabolic and autoimmune diseases. Therefore, matching a ligand to an orphan GPCRs, the process of de-orphanizing, is of great importance in order to better understanding human physiology as well as to dissect the molecular mechanism governing the involvement of these receptors in human pathology. GPR84 is an example of an orphan GPCR (Sharman et al., 2011), although it is widely accepted that medium‐chain fatty acids (MCFAs) can bind to and activate this receptor with modest potency. GPR84 is a Gi‐coupled class A GPCR mainly expressed in immune cells and microglia in the brain (Wojciechowicz & Ma'ayan, 2020). GPR84 has been shown to be an attractive target in pro‐inflammatory conditions (Gagnon et al., 2018; Suzuki et al., 2013; Vermeire et al., 2017; Wojciechowicz & Ma'ayan, 2020) and efforts have been made to discover GPR84 antagonists. In this study Marsango et al. address two key questions in GPR84 biology and pharmacology: 1. how GPR84 expression profile correlates with physiological and pathological conditions? and 2. which ligands can be used as tool compounds to study the function and biology of this receptor? Regarding the first question, GPR84 overexpression in immune cells in a range of pro‐inflammatory disorders renders it a promising target in inflammatory and fibrotic conditions, including neuroinflammation (Audoy‐Remus et al., 2015), with ongoing clinical trials in idiopathic pulmonary fibrosis (Labéguère et al., 2014). GPR84 has been additionally proposed to be a potential biomarker in different inflammatory diseases (Arijs et al., 2011; Planell et al., 2017). Some studies have also reported GPR84 involvement in pain, atherosclerosis, and even metabolic disorders (Nicol et al., 2015, Audoy‐Remus et al., 2015, Du Toit et al., 2018). Regarding the second question, there is still a lot to be done in respect to tool compounds to study the function of this receptor towards clinical validation, as well as radiopharmaceuticals, including potential PET ligands, and suitable antibodies. Recent work has shown distinct functional outcomes of agonist ligands (Pillaiyar et al., 2018) with biased properties which can help to better elucidate the molecular pharmacology of this receptor. In addition, several GPR84 ligands have been described as well as GPR84 knockout mice. Among these ligands are orthosteric agonists such as alkylpyrimidine‐4,6‐diol derivatives (Liu et al., 2016; Zhang et al., 2016) and embelin (2,5‐dihydroxy‐3‐undecyl‐1,4‐benzoquinone) which is a natural product derived from the plant Embelia ribes (Gaidarov et al., 2018) which agonizes GPR84 but, interestingly, blocks the chemokine receptor CXCR2 and the adenosine A3 receptor (Gaidarov et al., 2018). IM (3,3′‐methylenebis‐1H‐indole) has been identified as a positive allosteric modulator of GPR84, a metabolite produced in vivo from indole‐3‐carbinol, which is present at high levels in some vegetables including broccoli and kale (Wang, Schoene, Milner, & Kim, 2012, Köse et al., 2020). GPR84 antagonists include a series of dihydropyrimidinoisoquinolinones (Labéguère et al., 2014), which behave as non‐competitive antagonists of GPR84 (Labéguère et al., 2020). From these series of compounds, GLPG1205 progressed into clinical development for the potential treatment of ulcerative colitis although it did not demonstrate sufficient efficacy (Labéguère et al., 2020). Overall, GPR84 is a promising target to exploit and the investment in better tools to study its function in both disease and physiological settings will likely potentiate drug discovery campaigns against this orphan GPCR. Check the original article at here! #GPCR #DrGPCR#Ecosystem

September 2022 Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs Interestingly, RGS (Regulators of G protein signaling) proteins, which negatively regulate GPCR signaling

Unexpectedly, Class A G protein-coupled receptors (GPCRs), a large class of signaling proteins exemplified

August 2022 "GPR21 is an orphan and constitutively active receptor belonging to the superfamily of G-Protein GPR21 couples to the Gq family of G proteins and is expressed in macrophages.

Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors expressed in tumors G protein-coupled receptors (GPCRs) are the largest family of human proteins. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and Phenotypic characterization suggests these mutations induce perturbation of G protein activation and/

G protein-coupled receptors (GPCRs) are crucial receptors that regulate a wide range of physiological

Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled

October 2022 "Understanding the activation of G protein-coupled receptors (GPCRs) is of paramount importance

Previous research showed that activation of Gq/11 proteins by G-protein coupled receptors has pro-nociceptive

Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of ligand type and receptor activation state G protein-coupled receptors (GPCR) are the largest family of

Genome-wide identification of 216 G protein-coupled receptor (GPCR) genes from the marine water flea Diaphanosoma celebensis G protein-coupled receptors (GPCRs) are considered to have originated from early

In this review, we focus on recent advances in G-protein-coupled receptor (GPCR) targets.

November 2022 "Despite the growing number of G protein-coupled receptor (GPCR) structures, only 39 structures

G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase However, the rank order of the agonists for G protein- and GRK2-M3R interaction was the same, suggesting that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements

September 2022 "Heterotrimeric G-protein transducin, Gt, is a key signal transducer and amplifier in The only other farnesylated G-protein γ-subunit, Gγ11 (Gng11), is expressed in multiple tissues but not