October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte Cardiac contractility, essential to maintaining proper cardiac output and circulation, is regulated by G protein-coupled 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

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.

A role for BET proteins in regulating basal, dopamine-induced and cAMP/PKA-dependent transcription in One candidate effector of PKA-dependent transcriptional regulation is the BET protein Brd4. However, it is unknown whether BET proteins, or Brd4 specifically, are involved in transcriptional activation Here, we demonstrate that in adult rats, inhibition of BET proteins with the bromodomain inhibitor JQ1 Our findings identify the BET protein family, and Brd4 in particular, as novel regulators of basal and

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 ( Novitzky-Basso and Rot, 2012 ). Erythrocytes are terminally differentiated anuclear cells with no transcription and limited translation. Accordingly, within the erythroid lineage ACKR1 expression occurs first and is the highest in erythroblasts ( Duchene et al., 2017 ). Additionally, ACKR1 expression characterizes venular endothelial cells (ECs) ( Pruenster et al., 2009 ; Thiriot et al., 2017 ), including those lining bone marrow (BM) sinusoids ( Duchene et al., 2017 ). This well-established, distinctive pattern of cell expression has been directly challenged by a publication purporting ACKR1 expression in mouse BM by macrophages, but not erythroblasts and ECs, suggesting that macrophage ACKR1 engages its non-cognate ligand CD82 on hematopoietic stem cells (HSCs) to maintain their quiescence ( Hur et al., 2016 ). In light of the extensive literature, these findings have been particularly provocative, as this was the first description of ACKR1 expression by any leukocyte type and, if correct, would change current concepts of ACKR1 involvement in pathophysiology. The reported ACKR1 expression by macrophages in Hur et al. relied on using commercial anti-ACKR1 antibody FAB6695, which has neither been validated by the manufacturer nor by the authors. This prompted us to investigate the specificity of FAB6695 and scrutinize the apparent ACKR1 expression in BM macrophages" Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation of Adhesion Receptor GPR97 "Adhesion G-protein-coupled receptors (aGPCRs)-a major family of GPCRs-play Although it has been established that the palmitoylation of the C-terminal Go protein is essential for overall conformation of GPR97 is preferred to be fully active when interacting with palmitoylated Go protein provides mechanistic insights into the regulation of aGPCRs via post-translational modifications of the Go protein

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

cryogenic-electron microscopy (cryo-EM) is used extensively to determine structures of activated G 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 Here, we address this shortcoming by exploring different fusion protein designs, which lead to structures

October 2022 "Background: Uncoupling proteins (UCPs) are unpaired electron carriers that uncouple oxygen 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

October 2022 Design and validation of recombinant protein standards for quantitative Western blot analysis radioligand binding assays with antibody-antigen interaction-based approaches for quantitative analysis of G protein-coupled receptor (GPCR) levels requires the use of purified protein standards containing the antigen. Results: Here we generated highly soluble and stable recombinant protein constructs GST-CB1414-472 and -473 of the mouse CB1 receptor that corresponds to residues 442-472 in the human homolog.

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

Significant advancements in the cellular biology of G protein-coupled receptors (GPCRs) about a novel This study, published in Nature Chemical Biology, highlights the role of the chaperone protein DNAJC13 By employing this biosensor, the research team identified 492 genes that significantly influence DOR During this process, APEX2 can label proteins in the vicinity, allowing the capture of a snapshot of After the labeling reaction, the researchers purified and biotinylated proteins (those that have been

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

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

September 2022 "The GPR15 receptor is a G protein-coupled receptor (GPCR), which is activated by an endogenous GPR15L(71-81) are used as pharmacological tool compounds to delineate the GPR15 receptor-mediated Gα protein signalling using a G protein activation assay and second messenger assay conducted on living cells.

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.

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 "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 migration assay, performed on macrophages derived from both the THP-1 cell line and human peripheral blood monocytes

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

September 2022 Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative to its N-terminal fragment 1 to 36 "The parathyroid hormone (PTH)-related protein (PTHrP) is indispensable amino acids, our current understanding on how endogenous PTHrP transduces signals through its cognate G-protein together, our results contribute to a better understanding of the biased signaling process of a native protein

the activity of the Gα subunit and resulting in negative regulation of MOR downstream signaling[3, 4] that is coupled to the receptor and leading to a decrease in dopamine signaling[4, 5]. Pharmacol Rev, 2002. 54(3): p. 527-59. https://pubmed.ncbi.nlm.nih.gov/12223533/ 4. Wang, Q., L.Y. Cell, 2021. 184(4): p. 931-942.e18. https://pubmed.ncbi.nlm.nih.gov/33571431/ 6. Genomics, 2021. 113(4): p. 2134-2144. https://pubmed.ncbi.nlm.nih.gov/33845140/

August 2022 Gαs and Gαq/11 protein coupling bias of two AVPR2 mutants (R68W and V162A) that cause nephrogenic AVPR2 is a kind of G protein coupled receptor (GPCR) and mainly couples with Gαs protein leading to cAMP Recent studies showed that some AVPR2 mutations could cause biased Gαq/11 protein coupling rather than In this study, R68W and V162A were analyzed to whether they show a bias to Gαs or Gαq/11 proteins. R68W showed bias to coupling with Gαq/11 protein rather than V162A and wild-type receptor.

October 2022 "G protein-coupled receptors (GPCRs) are of considerable interest due to their importance in the cardiovascular system of the three most important GPCR signaling effectors: heterotrimeric G proteins We will first summarize their prominent roles in GPCR pharmacology before transitioning into less well-explored

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

September 2022 Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs Interestingly, RGS (Regulators of G protein signaling) proteins, which negatively regulate GPCR signaling Our analysis further supports the putative function of RGS proteins, particularly RGS20, in cancer."

October 2022 Use of CRISPR/Cas9-edited HEK293 cells reveals that both conventional and novel protein kinase C isozymes are involved in mGlu5a receptor internalization "The internalization of G protein-coupled phosphorylation site in the receptor C-tail, both showed that PKC isozymes facilitate approximately 40% GPCR kinase 2 and 3 (GRK2 and GRK3) KO cells, and a receptor containing a mutated putative adaptor protein 2 (AP-2) interaction motif, we demonstrate that internalization of rat mGlu5a is mediated by Gαq/11 proteins

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. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and Phenotypic characterization suggests these mutations induce perturbation of G protein activation and/

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