September 2022 "Metabotropic γ-aminobutyric acid receptor (GABABR), a class C G protein-coupled receptor (GPCR) heterodimer, plays a crucial role in the central nervous system. Cryo-electron microscopy studies revealed a drastic conformational change upon activation and a unique G protein (GP) binding mode. However, little is known about the mechanism for GP coupling and activation for class C GPCRs. Here, we use molecular metadynamics computations to predict the mechanism by which the inactive GP induces conformational changes in the GABABR transmembrane domain (TMD) to form an intermediate pre-activated state. We find that the inactive GP first interacts with TM3, which further leads to the TMD rearrangement and deeper insertion of the α5 helix that causes the Gα subunit to open, releasing GDP, and forming the experimentally observed activated structure. This mechanism provides fresh insights into the mechanistic details of class C GPCRs activation expected to be useful for designing selective agonists and antagonists." Read more at the source #DrGPCR #GPCR #IndustryNews

Treatment of cells with YM failed to inhibit signaling by these PM-restricted αqQ209L.

Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced Here, we show that the gut IEL GLP-1 receptor (GLP-1R) is not required for enteroendocrine L cell GLP anti-inflammatory actions of GLP-1RAs require the gut IEL GLP-1R to selectively restrain local and systemic T cell-induced are mediated by the suppression of gut IEL effector functions linked to the dampening of proximal T cell These data reposition key roles of the L cell-gut IEL GLP-1R axis, revealing mechanisms linking GLP-1R

Inhibition of autophagy by 3-methyladenine or interference of ATG5 or ATG7 attenuated HBx-induced cell

of HH, the second effect of FU leads to the local enrichment of SMO in the most basal domain of the cell

., of the University of Oxford , has joined Exscientia as Chief Scientist of Biologics AI.

Extensive efforts of structural biology have been made on the study of GPCRs.

Electron cryo-microscopy (cryo-EM) is a powerful technique for the structural characterization of biological Structural characterization of biologics, such as vaccines, viral vectors, and gene therapy agents, has

September 2022 "The activation of phospholipase C (PLC) is thought to have a key role in the cardiomyocyte response to several different hypertrophic agents such as norepinephrine, angiotensin II and endothelin-1. PLC activity results in the generation of diacylglycerol and inositol trisphosphate, which are downstream signal transducers for the expression of fetal genes, increased protein synthesis, and subsequent cardiomyocyte growth. In this article, we describe the signal transduction elements that regulate PLC gene expression. The discussion is focused on the norepinephrine- α1-adrenoceptor signaling pathway and downstream signaling processes that mediate an upregulation of PLC isozyme gene expression. Evidence is also indicated to demonstrate that PLC activities self-regulate the expression of PLC isozymes with the suggestion that PLC activities may be part of a coordinated signaling process for the perpetuation of cardiac hypertrophy. Accordingly, from the information provided, it is plausible that specific PLC isozymes could be targeted for the mitigation of cardiac hypertrophy." Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Visual phototransduction is the most extensively studied G protein-coupled receptor (GPCR) signaling pathway because of its quantifiable stimulus, non-redundancy of genes, and immense importance in vision. We summarize recent discoveries that have advanced our understanding of rod outer segment (ROS) morphology and the pathological basis of retinal diseases. We have combined recently published cryo-electron tomography (cryo-ET) data on the ROS with structural knowledge on individual proteins to define the precise spatial limitations under which phototransduction occurs. Although hypothetical, the reconstruction of the rod phototransduction system highlights the potential roles of phosphodiesterase 6 (PDE6) and guanylate cyclases (GCs) in maintaining the spacing between ROS discs, suggesting a plausible mechanism by which intrinsic optical signals are generated in the retina." Read more at the source #DrGPCR #GPCR #IndustryNews

Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs). The experimental structure of these receptors has yet to be determined, and key-residues controlling their function remain mostly unknown. We designed an integrative approach to improve comparative modeling of TAS2Rs. Using current knowledge on class A GPCRs and existing experimental data in the literature as constraints, we pinpointed conserved motifs to entirely re-align the amino-acid sequences of TAS2Rs. We constructed accurate homology models of human TAS2Rs. As a test case, we examined the accuracy of the TAS2R16 model with site-directed mutagenesis and in vitro functional assays. This combination of in silico and in vitro results clarifies sequence-function relationships and proposes functional molecular switches that encode agonist sensing and downstream signaling mechanisms within mammalian TAS2Rs sequences. Read full article

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4 WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild type CXCR4 and a previously identified WHIM syndrome mutant, R334X. The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation. This increase is at least partially due to a significant decrease in agonist-promoted phosphorylation, β-arrestin binding, and endocytosis of S339fs5 and R334X compared to wild type CXCR4. Interestingly, there were also significant differences in receptor degradation, with S339fs5 having a very high basal level of degradation compared to that of R334X and wild type CXCR4. In contrast to wild type CXCR4, both R334X and S339fs5 were largely insensitive to CXCL12-promoted degradation. Moreover, while basal and agonist-promoted degradation of wild type CXCR4 was effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants. Taken together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced signaling, reduced phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected by antagonist treatment. Read full article

passion and connect with your amazing peers to dive into the cutting-edge advancements in adhesion GPCR biology Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell research position Adhesion GPCRs The G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell regulate a wide spectrum of endocrine tumors G protein coupled receptor transcripts in human immune cells

al. for their fantastic work on Germline mutations in a G protein identify signaling cross-talk in T cells 2024 Get ready to connect with your peers and explore the cutting-edge advancements in adhesion GPCR biology using polymer-encapsulated nanodiscs Google DeepMind And Isomorphic Labs Are Making Rapid Progress In Biology Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell

GPCR Signaling Measurement and Drug Profiling with an Automated Live-Cell Microscopy System. and more Cytotoxicity-related effects of imidazolium and chlorinated bispyridinium oximes in SH-SY5Y cells in Oncology and Immunology Vasoactive intestinal peptide receptor 2 signaling promotes breast cancer cell Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. of Molecular Pharmacology, Discovery Biology Staff Scientist/Senior Staff Scientist, Disease Biology

October 23-25, 2024 Engage with your peers and delve into the latest developments in adhesion GPCR biology for its First-in-class GPR68 Inhibitor Asengeprast (FT011) AlphaProteo generates novel proteins for biology Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Molecular Pharmacology - The Hauser Group NEW Postdoctoral Scholar – iPSC in cardiac and endothelial cell Class A GPCR-biased ligands GPCRs in Cardiology, Endocrinology, and Taste CRTC1 in Mc4r-expressing cells

Mexico City Dates:  October 23-25, 2024 Connect with peers and delve into cutting-edge adhesion GPCR biology more Selenomethionine Promotes Milk Protein and Fat Synthesis and Proliferation of Mammary Epithelial Cells for GPCR Papers NEW Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR , 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery NEW September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics

Nicholas Kapolka , Geoffrey Taghon , and Daniel Isom  for their research on Advances in yeast synthetic biology for human GPCR biology and pharmacology Dr. from October 23-25, 2024, to connect with fellow scientists and explore the latest in adhesion GPCR biology protein-coupled receptor (GPCR) gene variants and human genetic disease Advances in yeast synthetic biology for human G protein-coupled receptor biology and pharmacology Industry News Muscarinic drugs breathe

Soluble cyclase-mediated nuclear cAMP synthesis is sufficient for cell proliferation. Methods & Updates in GPCR Research Mapping of structural arrangement of cells and collective calcium SLAS 2023 Building Biology in 3D Symposium. Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. and GPCRs Chief of Staff Postdoctoral Fellow, Biochemical And Cellular Pharmacology Project Leader, Biology

therapeutically exploit GPCRs (Physiology’s ‘Swiss Army Knife’) vast repertoire of ways to control cell Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract Intracellular

Prize in Physiology or Medicine went to George Herbert Hitchings, Sir James Whyte Black, and Gertrude Belle Rodbell for their discovery of G-proteins and the role of these proteins in signal transduction in cells .[40–46] In his work, Rodbell demonstrated that signal transduction through the cell membrane involves transduction that requires GTP is G-protein and was the first to isolate it through his work on leukemia cells Non-traditional roles of G protein-coupled receptors in basic cell biology.

August 2022 "GPCRs in Medicinal Chemistry Event 8th RSC / SCI symposium on GPCRs in Medicinal Chemistry Dates Wednesday-Friday, 5th-7th October 2022 Place Evotec Campus Levi-Montalcini, Verona, Italy Downloads and Links Registration closing dates: 6th September – registration against invoice (bank transfers): Tuesday, 6th September 30th September – online registration (card payments)" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 RAB-Symposium - Regulatory Autoantibodies Targeting GPCRs. September 15-16, 2022. Lübeck, Germany. Hybrid meeting. "Dear Sir or Madam, dear Colleagues, It gives me great pleasure to announce the fourth hybrid symposium on regulatory autoantibodies targeting G-protein-coupled receptors (GPCRs) in Lübeck. GPCRs are involved in a variety of physiological and pathophysiological processes. So far, numerous therapeutics targeting GPCRs have been developed, with a focus on small molecules and monoclonal antibodies for the treatment of cancer, infections, metabolic disorders or inflammatory diseases. Recently, functional autoantibodies targeting GPCRs have been associated with various disease-specific manifestations, highlighting a potential new area for therapeutic intervention. Therefore, the aim of this symposium is to bring together the current knowledge on the role of autoantibodies targeting GPCRs in various diseases, such as cardiovascular diseases, renal diseases, autoimmune diseases such as systemic sclerosis or systemic lupus erythematosus. In addition, one aim is to bring together the mode of action of autoantibodies in immune regulation and pathogenesis." Read more at the source #DrGPCR #GPCR #IndustryNews

Discovery on Target (DOT) highlights advances in current and emerging “hot” targets and technologies, as well target validation strategies for the discovery and development of novel therapeutic agents ranging from biologics

August 2022 "WELCOME 4GPCRnet meeting bringing together four of the biggest GPCR networks in Europe for a joint meeting in Leipzig. Four of the biggest European networks on GPCR research (COST Actions Adher’n Rise and ERNEST plus DFG-funded SFB1423 and FOR2372) have joined forces to organize an international meeting, which will take place from 26th-29th September 2022 in the beautiful city of Leipzig in Germany. We aim to connect renowned international experts of the field with early career ‘rising stars’. The event will take place in the heart of Leipzig, which offers a colorful mixture of culture and vivid social life." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "We are happy to announce you our 2nd IRN i-GPCRnet meeting that will be held at the University of Wurzburg (Germany) from september 30th to october 1rst." Read more at the source #DrGPCR #GPCR #IndustryNews

., for their study on Cell swelling enhances ligand-driven β-adrenergic signaling ✨ Reserve Your seat Connect with your colleagues and immerse yourself in the most recent advancements in adhesion GPCR biology This technique for studying cell receptors could have sweeping implications for drug development DeepCure Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars plate homeostasis through IHH Signaling GPCR Activation and Signaling Illuminating GPCR trafficking Cell

of Mexico City to connect with fellow scientists and delve into the latest advances in adhesion GPCR biology Kv7 channels via Gi/o protein signalling and modulates excitability of human induced pluripotent stem cell-derived Phytocannabinoids in neuromodulation: From omics to epigenetics The impact of nanobodies on GPCR structural biology , 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal