September 2022 Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative coupled receptor (GPCR), the PTH type 1 receptor (PTHR), is largely derived from studies done with its demonstrate using various fluorescence imaging approaches at the single cell level to measure kinetics of (i) receptor activation, (ii) receptor signaling via Gs and Gq, and (iii) receptor internalization and recycling native protein hormone acting in conjunction with a GPCR."

of Adhesion Receptor GPR97 "Adhesion G-protein-coupled receptors (aGPCRs)-a major family of GPCRs-play The orphan receptor GPR97, activated by glucocorticoid stress hormones, is a prototypical aGPCR. Go's efficient engagement with the active GPR97, the detailed allosteric mechanism remains to be clarified analyzed by Markov state models revealed that the overall conformation of GPR97 is preferred to be fully active when interacting with palmitoylated Go protein.

September 2022 "GPCR signaling and function depend on their associated proteins and subcellular locations Besides G-proteins and β-arrestins, 14-3-3 proteins participate in GPCR trafficking and signaling, and they connect a large number of diverse proteins to form signaling networks. signals could implicate either GPCR/14-3-3 complex dissociation or the complex undergoing a degradation process

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 protein 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.

November 2022 "Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure of aGPCR activation. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling

CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal Stability to the Serotonin 1A Receptor "G protein-coupled receptors (GPCRs) constitute the largest class of membrane proteins that transduce The serotonin1A receptor is a crucial neurotransmitter receptor in the GPCR family involved in a multitude In addition, we showed that membrane cholesterol stabilizes the serotonin1A receptor against thermal consensus (CRAC) motif in transmembrane helix 2 in conferring the thermal stability of the serotonin1A receptor

Herein, we identified GPR108, a GPCR protein described in innate immune system, is a potential therapeutic Notably, TNFα activation of NF-κB was totally impaired after GPR108 knockout. Furthermore, in vitro and in vivo assays demonstrated that GA was dependent on GPR108 to exert anti-cancer activity

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. effectors, activate downstream pathways that often modulate hallmark mechanisms of cancer. We also discovered that no single receptor drives this pattern, but rather multiple receptors contain Phenotypic characterization suggests these mutations induce perturbation of G protein activation and/

G protein-coupled receptors (GPCRs) are among the most promising drug targets. They often form homo- and heterodimers with allosteric cross-talk between receptor entities, which contributes Specifically controlling the activity of GPCR dimers with ligands is a good approach to clarify their The data support the inference that they act at the active interface between both transmembrane domains transmembrane domain, which also controls the constitutive activity of the GABAB receptor.

October 2022 "G protein-coupled receptors (GPCRs) play critical roles in human physiology and are one allosteric sites and significantly enhanced our understanding of how allosteric ligands interact with receptors structures in complex with small-molecule allosteric ligands in terms of the location of allosteric pockets, receptor-ligand

Considering the central role of the serotonin 5-HT2A receptor in the distinct effects of psychedelics

One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled receptor L3 (ADGRL3, former name: latrophilin-3, LPHN3), the other on chromosome 3p26.3 in the region

Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and their G protein-coupled receptors in the oriental fruit moth Grapholita molesta The oriental fruit moth Grapholita molesta is Neuropeptides and their specific receptors (primarily G protein-coupled receptors, GPCRs) regulate multiple

Objective: The goal of this study was to determine the glucometabolic effects of acute activation of receptor (Gs-DREADD or GsD) selectively in skeletal muscle. and CRF2 receptor) and studied the acute metabolic effects of activating these receptors in vivo by The acute metabolic effects following agonist activation of β2-adrenergic and, potentially, CRF2 receptors Conclusions: Selective activation of Gs signaling in SKM causes an acute increase in blood glucose levels

September 2022 "Melanocortin 4 receptor (MC4R) is part of the leptin-melanocortin pathway and plays an We have previously reported that the MC4R forms homodimers, affecting receptor Gs signaling properties NanoBRETTM studies to determine protein–protein interaction were conducted, confirming decreased homodimerization capacities of chimeric receptors in HEK293 cells. Gq/11 signaling of chimeric receptors was analyzed using luciferase-based reporter gene (NFAT) assays

Clayton from BioTek Instruments talk about automated micro-plate-based methods for quantifying #GPCR activation

2022 "Abstract Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein

This communication involves the ligand-mediated control of cell surface receptors that then direct their has been placed on the ability of these therapeutics to modulate diseases by acting at cell surface receptors both at the cell surface membrane and in the intracellular domain dictate and condition long-term GPCR activities associated with the regulation of protein expression patterns, cellular stress responses and DNA integrity these receptorsomes (often in the absence of typical cell surface ligands) to control complex cellular activities

Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligands "G-protein coupled receptors (GPCRs) have been largely targeted in a wide range of diseases, but few therapies We selected the adenosine receptor 2B (A2BAR), specifically expressed in cancer cell lines compared with Fluorescent probes allowed semi-quantitative receptor mapping in living cells and validated the specific As well, fluorescent ligands were effective at monitoring real-time A2BAR receptor labeling using live-imaging

of cannabinoid CB1 receptor density in cell membranes: an alternative to radioligand binding methods receptor (GPCR) levels requires the use of purified protein standards containing the antigen. GPCRs in general and cannabinoid CB1 receptor in particular show a progressive tendency to aggregate GST-CB1414-442 containing much of the human CB1 receptor C-terminal tail for use as standard and negative Estimated values of CB1 receptor density obtained by quantitative Western blot were of the same order

2022 GPCRs steer G i and G s selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors "Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of Gs, Gi, or Gq proteins. Here, we report the structures of the serotonin receptors 5-HT4, 5-HT6, and 5-HT7 with Gs, and 5-HT4 by class A GPCRs and extend the basis of ligand recognition at serotonin receptors."

β-arrestins (βarrs) play multifaceted roles in the function of G protein-coupled receptors (GPCRs). βarrs However, the effects of the C tail- and TM core-mediated interactions on the conformational activation Our NMR analyses demonstrated that while the C tail-mediated interaction alone induces partial activation , in which βarr exists in equilibrium between basal and activated conformations, the TM core- and the The conformation-selective antibody, Fab30, promotes partially activated βarr into the activated-like

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein

Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR)

Currently, attention was mainly paid to biased signaling modulators targeting G protein-coupled receptors The biased signaling modulation of non-GPCR receptors has yet to be exploited. Toll-like receptor 4 (TLR4) is one such non-GPCR receptor, which involves MyD88-dependent and TRIF-dependent Small molecules biasedly modulating the TLR4 signaling axis not only provide probes to fine-tune receptor modulators of TLR4 would provide insight for the future development of biased modulators for other non-GPCR receptors

September 2022 "G protein‐coupled receptors (GPCRs) are valuable therapeutic targets for many diseases We hypothesized that there is a common set of receptor interactions made by ligands of diverse structures β2AR structures, generating ca 75 000 docking poses and predicted all atomic interactions between the receptor ML analysis in human understandable form allowed us to construct an exquisitely detailed structure‐activity relationship that identifies small changes to the ligands that invert their pharmacological activity

February 2022 Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Research on cancer therapies focuses on processes such as angiogenesis, cell signaling In 2008 (and for the first time in the clinic), the therapeutic benefits of the β-adrenergic receptor