September 2022 "Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipids have been shown to stabilize In this work, we applied MD simulations supported by native mass spectrometry (nMS) to study lipid interactions We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR Specifically, we find the PI(4,5)P2 lipids to have a higher affinity toward the inactive conformation

cholesterol, a prominent component of the plasma membrane, limits the ability of GPCRs to scramble lipids This mechanism may explain the inability of GPCRs to scramble lipids at the plasma membrane."

September 2022 Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism calibrate glucagon-like peptide 1 (GLP-1) bioavailability, thereby regulating systemic glucose and lipid metabolism. -1R) is not required for enteroendocrine L cell GLP-1 secretion and glucose homeostasis nor for the metabolic

October 2022 Membrane Lipids Are an Integral Part of Transmembrane Allosteric Sites in GPCRs: A Case Ligands must first partition into the surrounding membrane and take lipid paths to these sites. Remarkably, a significant part of the bound ligands appears exposed to the membrane lipids. Using classical and enhanced molecular dynamics simulations, we show that membrane lipids are critical Our results demonstrate the significance of incorporating membrane lipids as an integral component of

August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid

sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid

the effects of THC and CBD on the differentiation of MECs by assessing changes in cellular viability, lipid accumulation, and gene and protein expression of major milk protein and lipid synthesizing markers. We hypothesized that THC and CBD will negatively impact the synthesis of milk proteins and lipids, as well as lipid markers in HC11 cells. Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP) , lipid

ciliary membrane models, respectively, to study the interactions of SMO with cholesterol and other lipid

GHSR1a now extend to regulation of neurogenesis, learning and memory, gastrointestinal motility, glucose/lipid metabolism, the cardiovascular system, neuronal protection, motivational salience, and hedonic feeding

September 2022 "The complement fragment C5a is one of the most potent proinflammatory glycoproteins liberated by the activation of the biochemical cascade of the complement system. C5a is established to interact with a set of genomically related transmembrane receptors, like C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2) with comparable affinity. The C5aR1 is a classical G-protein-coupled receptor (GPCR), whereas C5aR2 is a nonclassical GPCR that tailors immune cell activity potentially through β-arrestins rather than G-proteins. Currently, the exact function of the C5aR2 is actively debated in the context of C5aR1, even though both C5aR1 and C5aR2 are coexpressed on myriads of tissues. The functional relevance of C5aR2 appears to be context-dependent compared to the C5aR1, which has received enormous attention for its role in both acute and chronic inflammatory diseases. In addition, the structure of C5aR2 and its interaction specificity toward C5a is not structurally elucidated in the literature so far. The current study has attempted to close the gap by generating highly refined model structures of C5aR2, respectively in free (inactive), complexed to C-terminal peptide of C5a (meta-active) and the C5a (active), embedded to a model palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. The computational modeling and the 1.5-μs molecular dynamics data presented in the current study are expected to further enrich the understanding of C5a-C5aR2 interaction compared to C5a-C5aR1, which will surely help in elaborating the currently debated biological function of C5aR2 better in the foreseeable future." Read more at the source #DrGPCR #GPCR #IndustryNews

Classified GPCR News from September 16th to 22nd, 2024 Industry News Inversago Pharma’s INV-347 improves metabolic Progress In Biology And Drug Discovery GLP-1/FGF21 dual agonist ZT-003 shows promising results for metabolic GPCRs in Oncology and Immunology GPR37 promotes colorectal cancer against ferroptosis by reprogramming lipid metabolism via p38-SCD1 axis Methods & Updates in GPCR Research GPCRSPACE: A New GPCR Real Expanded

synaptic events, exocytosis, transcriptional regulation, and more, PKA signaling regulates cellular metabolism afferent and peripheral efferent signals that link specific neural cell populations to the regulation of metabolic Mouse models have provided invaluable information on the roles for PKA subunits in brain and key metabolic Variants identified in PKA subunit genes cause Cushing syndrome that is characterized by metabolic dysregulation

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. The physiological activities of UCPs have been hotly contested, and the involvement of UCPs in the pathogenesis and progression of diabetes mellitus is among the greatest concerns. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who are experiencing oxidative stress. Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through protein uncoupling." Read more at the source #DrGPCR #GPCR #IndustryNews

March 2022 Inversago Pharma Announces Dosing of First Participant with Metabolic Syndrome in Phase 1B unique portfolio of CB1 inverse agonists, announced today the dosing of the first participant with metabolic pharmacokinetics and safety profile of Inversago’s lead molecule, INV-202, on a targeted population with metabolic

October 2022 Recurrent hypoglycemia increases hepatic gluconeogenesis without affecting glycogen metabolism Whether and how RH affects responses within metabolically important peripheral organs to counterregulatory Objective: To study the effects of RH on metabolic pathways associated with glucose counterregulation G-protein coupled receptors (GPCRs), their inhibitory regulators and downstream enzymes catalyzing glycogen metabolism

expressed by SKM at relatively high levels (β2-adrenergic receptor and CRF2 receptor) and studied the acute metabolic The acute metabolic effects following agonist activation of β2-adrenergic and, potentially, CRF2 receptors The acute metabolic effects of UCN2 were not mediated by SKM Gs signaling.

However, our knowledge of how GPCRs regulate liver metabolism and fibrosis in the different cell types

September 2022 Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites

Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on the skeletal metabolism

Patrick Sexton, and Matthew Belousoff et al. for their work on Lipid-Dependent Activation of the Orphan April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join Dr. GPCR Founder Dr. Yamina Berchiche at the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Single-Molecule Level Pharmacological characterization of seven human histamine H3 receptor isoforms Lipid-Dependent Oncology and Immunology TIPE proteins control directed migration of human T cells by directing GPCR and lipid

Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic ligand interactions and stability, the binding site structure, and how all of these are affected by lipid work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors in three lipid Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound

in GPCR Research High-throughput G protein-coupled receptor-based autocrine screening for secondary metabolite Reviews, GPCRs, and more Class B1 GPCRs: Insights into Multi-Receptor Pharmacology for the Treatment of Metabolic Receptor Influence of the Water Model on the Structure and Interactions of the GPR40 Protein with the Lipid Membrane and the Solvent: Rigid versus Flexible Water Models Probing the energy landscape of the lipid

At the cellular level, the plasmatic membrane is a thin layer of lipids that surrounds the entire cell The physical barrier this lipid bilayer creates is dynamic and interactive, becoming the foundation for At this point, the lipid bilayer serves as a platform for the membrane recruitment of β-arrestins. Lipid molecules, such as phosphoinositides, can bind to specific domains of β-arrestins, promoting their Therefore the lipid composition of the bilayer can influence the kinetics and efficiency of β-arrestin

Using purified Fzd proteins reconstituted in lipid nanodiscs, we investigated the factors that promote Instead, Fzd-Dvl binding was enhanced by increased concentration of the lipid PI(4,5)P2, which is generated by Dvl-associated lipid kinases in response to Wnt and which is required for LRP5/6 phosphorylation.

In liposomes, opsin scrambles lipids at a unitary rate of >100,000 per second. Atomistic molecular dynamics simulations of opsin in a lipid membrane reveal conformational transitions This groove enables transbilayer lipid movement, conceptualized as the swiping of a credit card (lipid

eukaryotes is the phosphoinositide 3-kinase (PI3K) pathway, which plays fundamental roles in growth, metabolism We identify nanobodies that stimulated lipid kinase activity, block Ras activation, and specifically

mediated by human neutrophil expressed formyl peptide receptors Molecular recognition of niacin and lipid-lowering tissue morphogenesis TIPE proteins control directed migration of human T cells by directing GPCR and lipid Drug Discovery Chemistry April 5 - 10, 2024 | AACR Annual Meeting NEW April 22 - 23, 2024 | Endocrine Metabolic

First metabolic profiling of 4-n-nonylphenol in human liver microsomes by integrated approaches to testing and assessment: Metabolites, pathways, and biological effects. GPCR Jobs Postdoctoral Fellow - Molecular Dynamics Postdoc in lipid regulation of GPCRs Postdoctoral