September 2022 Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts To understand the basis of the ligand preferences of the receptors and to assist structure-based drug between the activated GALR2 and inactive hβ2AR was used to relate galanin binding to the movements of transmembrane (TM) helices and the G-protein interface."

meningitidis and identified 30 N-acyl amides with representative members serving as agonists of the G-protein coupled receptor (GPCR) S1PR4. During this process, we also characterized two mammalian N-acyl amides derived from the bovine medium

October 2022 "Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. /G13 engage receptor mainly through hydrophobic interaction. for understanding aGPCR activation and GPR110 signaling."

Human cells express over 800 G-protein-coupled receptors (GPCRs) to facilitate communication with the These receptors respond to a variety of signals by undergoing structural changes that activate internal separation from the receptor. to the dissociation of the G protein from the receptor. Physiological roles of G protein-coupled receptor kinases and arrestins.

Alterations in the expression and/or activity of brain G-protein-coupled receptors (GPCRs) such as dopamine functional role of kurarinone, an abundant lavandulated flavonoid in Sophora flavescens, on dopamine receptor

September 2022 "The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an Here, we provide evidence that activated human T cells express GLP-1R. Analysis of CD4+ T cells activated under T helper (Th) 1, Th2, Th17 and regulatory T (Treg) cell differentiation Taken together, the present data demonstrate that T cell activation triggers the expression of functional

September 2022 Microbial Metabolites Orchestrate a Distinct Multi-Tiered Regulatory Network in the Intestinal Epithelium That Directs P-Glycoprotein Expression "P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findings and discovered a role for intestinal HNF4α in P-gp regulation. These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp expression and highlight unappreciated connections between multiple pathways linked to colonic health." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 A2B Adenosine Receptor Enhances Chemoresistance of Glioblastoma Stem-Like Cells under Transcript and protein levels were determined by RT-qPCR and Western blot, respectively. we show for the first time that MRP3 expression is induced under hypoxia through the A2B adenosine receptor Downregulation of the A2B receptor decreases MRP3 expression and chemosensibilizes GSCs treated with These data suggest that hypoxia-dependent activation of A2B adenosine receptor promotes survival of GSCs

September 2022 GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome activation in macrophages "The putative medium-chain free fatty acid receptor GPR84 is a G protein-coupled receptor Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis GPR84 activation imposes pro-inflammatory properties in colonic macrophages through enhancing NLRP3 inflammasome activation, while the loss of GPR84 prevents the M1 polarization and properties of proinflammatory macrophages

"Protecting neurons from death during oxidative and neuroexcitotoxic stress is key for preventing cognitive serotonin receptor with no previously known neurological function. cells with NF-α1/CPE increased pERK 1/2 and pCREB levels which prevented a decrease in pro-survival protein recruited β-arrestin1 by forming numerous salt bridges and hydrogen bonds to ICL2 and ICL3, leading to activation Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB

September 2022 "Receptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that associate with different G protein–coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator of mineral ion homeostasis and bone metabolism Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we These data uncover a critical role of RAMPs in the activation and signaling of a GPCR that may provide

August 2022 "Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled receptor (GPCR) drug targets and also act as prototypical models for GPCR function.

One potent form of inhibition is mediated by the activation of two inhibitory G protein-coupled receptors Each of these receptors activates G protein-coupled inwardly rectifying potassium (GIRK) channels. The kinetics of the current induced by transient receptor activation is prolonged in each case. KEY POINTS: Inhibitory D2 and GABAB receptors modulate dopamine neuron activity through shared G protein-coupled Results demonstrate that the activity of either G protein-coupled receptor system must be considered

Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor, which couples to both Gq and Gi proteins, and the MT2 receptor, which We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10-100 inhibitor pertussis toxin or knockdown of the MT2 receptor by its specific siRNA.

August 2022 "The atypical chemokine receptor 1 (ACKR1) was discovered on erythrocytes as the Duffy blood group antigen ( Cutbush et al., 1950 ), also called Duffy-antigen/receptor for chemokines, or DARC (

counting techniques enable a precise determination of the intracellular abundance and stoichiometry of proteins Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate While early evidence for the role of oligomerization in receptor signaling came from ensemble biochemical the potential for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled receptor signaling."

October 2022 "Over three decades of research have provided thorough insights into G protein-coupled receptor Agonist activation of the β2-adrenoceptor (β2AR) causes its S-nitrosylation that is required for the receptor to internalize and desensitize. Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables β2AR nitric oxide (NO) signaling, renders mice resistant to bronchoconstriction, and protects mice from

August 2022 A NanoBRET-Based H 3 R Conformational Biosensor to Study Real-Time H 3 Receptor Pharmacology in Cell Membranes and Living Cells "Conformational biosensors to monitor the activation state of G protein-coupled receptors are a useful addition to the molecular pharmacology assay toolbox to characterize ligand efficacy at the level of receptor proteins instead of downstream signaling. We recently reported the initial characterization of a NanoBRET-based conformational histamine H3 receptor

2022 Comparative studies of AlphaFold, RoseTTAFold and Modeller: a case study involving the use of G-protein-coupled receptors "Neural network (NN)-based protein modeling methods have improved significantly in recent G-protein-coupled receptor (GPCR) proteins are particularly interesting since they are involved in numerous This work directly compares the performance of these novel deep learning-based protein modeling methods We collected the experimentally determined structures of 73 GPCRs from the Protein Data Bank.

October 2022 "The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system In the former, stimulation of Gs-coupled receptors leads to increases in contractility, whereas stimulation of Gq-coupled receptors modulates cellular survival and hypertrophic responses. well-studied effects of GPCRs in cardiac fibroblasts, focusing on key signaling events involved in the activation associated signaling machinery are localized in these cells with an emphasis on nuclear membrane-localized receptors

Acquired hypocalciuric hypercalcemia (AHH) is a rare disease caused by calcium-sensing receptor (CaSR This emphasizes the importance of the Gi/o (pertussis toxin-sensitive G proteins, whose βγ subunits activate CaSR, and (g) were likely to be conformational (i.e., recognizing and, thereby, stabilizing a unique active conformation of CaSR that activates Gq/11, activating phosphatidylinositol turnover, but not Gi/o).

A conserved intracellular allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs). Starting from vercirnon, an intracellular C-C chemokine receptor type 9 (CCR9) antagonist and previous To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs , thereby offering an unprecedented approach to modulate GPCR activity.

Phenylalanine 193 in Extracellular Loop 2 of the β 2-Adrenergic Receptor Coordinates β-Arrestin Interaction G protein-coupled receptors (GPCRs) transduce a diverse variety of extracellular stimuli into intracellular These receptors are the most clinically productive drug targets at present. components of receptor-effector interactions remain incompletely described. SIGNIFICANCE STATEMENT: The role of extracellular G protein-coupled receptor (GPCR) domains in mediating

October 2022 "The cAMP-dependent protein kinase (PKA) system represents a primary cell-signaling pathway PKA facilitates the actions of hormones, neurotransmitters and other signaling molecules that bind G-protein coupled receptors (GPCR) to modulate cAMP levels. peripheral efferent signals that link specific neural cell populations to the regulation of metabolic processes

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation Interestingly, there were also significant differences in receptor degradation, with S339fs5 having a phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected

rat striatal neurons The activity of striatal medium-spiny projection neurons is regulated by D1 and D2 dopamine receptors. The D1 receptor (D1R) is a Gαs/olf-coupled GPCR which activates a cAMP/PKA/DARPP-32 signalling cascade It is known that when Brd4 is activated by phosphorylation, it binds more readily to acetylated histones However, it is unknown whether BET proteins, or Brd4 specifically, are involved in transcriptional activation

G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular As activation and recruitment of effector proteins might influence each other, thorough analysis of bias Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase and analyzed arrestin3 binding to prestimulated M3 receptors to avoid differences in receptor phosphorylation that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements

2022 N-terminal alterations turn the gut hormone GLP-2 into an antagonist with gradual loss of GLP-2 receptor selectivity towards more GLP-1 receptor interaction "Background and purpose: To fully elucidate the regulatory role of the GLP-2 system in the gut and the bones, potent and selective GLP-2 receptor (GLP Searching for antagonist activity, we performed systematic N-terminal truncations of human GLP-2(1-33 To examine selectivity, COS-7 cells expressing human GLP-1 or GIP receptors were assessed for cAMP accumulation