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Biosensors for monitoring G protein-coupled receptors (GPCRs), the most drugged class of proteins in Their applications have continually expanded our understanding of this important protein class.

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

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 proteins, GPCR kinases (GRKs), and β-arrestins. We will first summarize their prominent roles in GPCR pharmacology before transitioning into less well-explored

Regulator G protein Signaling (RGS) proteins are critical components of the intracellular signaling pathways that mediate the effects of G protein-coupled receptors (GPCRs). between RGS proteins and GPCRs is mediated by a range of structural motifs, including the G protein-binding In conclusion, RGS proteins are essential modulators for the GPCR signaling mediated by G proteins, which Hepler, Cellular regulation of RGS proteins: modulators and integrators of G protein signaling.

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 protein (GP) binding mode.

The transport proteins that facilitate this process are classified as pump-like flippases and floppases Unexpectedly, Class A G protein-coupled receptors (GPCRs), a large class of signaling proteins exemplified

G protein-coupled receptors (GPCRs) are crucial receptors that regulate a wide range of physiological And A1, A2A, and CB2 activation by agonists has protective functions on noise- or drug-induced hearing and discuss the role of GPCR in the cochlea, such as stem cell fate, PCP, hearing loss, and hearing protection

October 2022 "Understanding the activation of G protein-coupled receptors (GPCRs) is of paramount importance field of cardiovascular medicine due to the critical physiological roles of these receptors and their prominence rapidly due to their biochemical tractability and their ability to recognize defined states of native proteins

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. GPR21 expression was evaluated at gene and protein level, the signalling pathway was investigated by

Most acquired genes are transmembrane proteins and cytokines, such as viral G protein-coupled receptors (vGPCRs), chemokines, and chemokine-binding proteins.

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

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 protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific

November 2022 "Despite the growing number of G protein-coupled receptor (GPCR) structures, only 39 structures These structures have been studied by protein mapping using the FTMap server, which determines the clustering of small organic probe molecules distributed on the protein surface. Mapping of Alphafold2 generated models of these proteins confirms that the same sites can be identified These sites cluster at nine distinct locations, and each can be found in many different proteins.

August 2022 "As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide Recently, AlphaFold2 has been developed to predict structure models of many functionally important proteins

October 2022 "Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled This review will focus in particular on pepducins designed from protease-activated receptors, C-X-C motif

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

protein-coupled receptors (GPCRs) in complex with G proteins or arrestins. However, applying it to GPCRs without signaling proteins remains challenging because most receptors lack In GPCR crystallography, inserting a fusion protein between transmembrane helices 5 and 6 is a highly the potential to broadly facilitate cryo-EM structure determination of GPCRs alone without signaling protein Here, we address this shortcoming by exploring different fusion protein designs, which lead to structures

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 genes coding for these proteins.

August 2022 "Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology. " Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Biased G protein-coupled receptor (GPCR) ligands, which preferentially activate G protein protein signaling. In contrast to Gpr3-deficient mice, G protein-biased GPR3 mice do not display elevated anxiety levels We further determined that G protein-biased signaling reduces soluble Aβ levels and leads to a decrease glial response that may limit amyloid plaque development in G protein-biased GPR3 AD mice.

G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor and memory, gastrointestinal motility, glucose/lipid metabolism, the cardiovascular system, neuronal protection In vitro and in vivo data suggest that GHSR1a heterodimerises with multiple G protein-coupled receptors , serotonin 2C, orexin, oxytocin and melanocortin 3 receptors (MCR3), as well as the MCR3 accessory protein

October 2022 "Visual phototransduction is the most extensively studied G protein-coupled receptor (GPCR published cryo-electron tomography (cryo-ET) data on the ROS with structural knowledge on individual proteins

August 2022 A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer "Adhesion G protein-coupled receptors (adhesion GPCRs), as a member of the G protein-coupled receptors (GPCRs) superfamily, have gradually entered the field of vision of

October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias protein-coupled receptor (GPCR) signaling. 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

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

October 2022 Focusing on the role of secretin/adhesion (Class B) G protein-coupled receptors in placental development and preeclampsia "Preeclampsia, a clinical syndrome mainly characterized by hypertension and proteinuria G protein-coupled receptors, the largest family of membrane proteins in eukaryotes and the largest drug Among them, the secretin/adhesion (Class B) G protein-coupled receptors are essential drug targets for Given the great value of the secretin/adhesion (Class B) G protein-coupled receptors in the regulation

October 2022 "Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and A comparison of Gq, Gs, Gi, G12 and G13 engagements with GPR110 reveals details of G-protein engagement Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework

In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while