August 2022 "As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-Gi1 complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-Å resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-Gi complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling." Read more at the source #DrGPCR #GPCR #IndustryNews

Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the

Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the

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 for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. (KI) approach to generate a mouse (in-host strain C57Bl/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R

August 2022 TAS2R supports odontoblastic differentiation of human dental pulp stem cells in the inflammatory microenvironment " Background: Inflammatory microenvironment promotes odontoblastic differentiation in human

October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled

August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence spectroscopy "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled

August 2022 "Histamine exerts its physiological functions through its four receptor subtypes. In this work, we report the subcellular localization of histamine receptor 2 (H2R), a G protein-coupled receptor (GPCR), which is expressed in a wide variety of cell and tissue types. A growing number of GPCRs have been shown to be localized in the nucleus and contribute toward transcriptional regulation. In this study, for the first time, we demonstrate the nuclear localization of H2R in lymphatic endothelial cells. In the presence of its ligand, we show significant upregulation of H2R nuclear translocation kinetics. Using fluorescently tagged histamine, we explored H2R-histamine binding interaction, which exhibits a critical role in this translocation event. Altogether, our results highlight the previously unrecognized nuclear localization pattern of H2R. At the same time, H2R as a GPCR imparts many unresolved questions, such as the functional relevance of this localization, and whether H2R can contribute directly to transcriptional regulation and can affect lymphatic specific gene expression. H2R blockers are commonly used medications that recently have shown significant side effects. Therefore, it is imperative to understand the precise molecular mechanism of H2R biology. In this aspect, our present data shed new light on the unexplored H2R signaling mechanisms. This article has an associated First Person interview with the first author of the paper." Read more at the source #DrGPCR #GPCR #IndustryNews

Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic Additionally, we detect a shortening of PC in PINK1 -deficient human cellular and mouse models of familial

September 2022 "The human sweet taste receptor is a heterodimeric receptor composed of two distinct G-protein-coupled To achieve this, we heterologously expressed human TAS1R2-VFT (hTAS1R2-VFT) in Escherichia coli .

In contrast, less is known about the expression and function of the GLP-1R in human T cells. Here, we provide evidence that activated human T cells express GLP-1R. the present data demonstrate that T cell activation triggers the expression of functional GLP-1R in human Given the high induction of GLP-1R in human iTreg cells, we hypothesize that GLP-1R+ iTreg cells play a key role in the anti-inflammatory effects ascribed to GLP-1R agonists in humans."

Humanity has always sought to live longer and for this, multiple strategies have been tried with varying maintaining good health since they have a substantial participation in a wide variety of processes of human the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human

September 2022 Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of

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

Obesity-induced changes in human islet G protein-coupled receptor expression: Implications for metabolic The human islet GPCRome is not a static entity, but one that is altered under pathophysiological conditions and, in this review, we have compared expression of GPCR mRNAs in human islets obtained from normal

We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR,

December 2021 "Early-stage studies of COVID-19 treatments from the likes of Vir Biotechnology Inc. and Trevena Inc. could offer potential new weapons against omicron and future viral variants. The omicron strain of the virus was first identified in South Africa in early November, and an existing treatment has already shown positive results in the lab. While vaccine-makers race to test their shots against the variant, the monoclonal antibody sotrovimab from Vir and partner GlaxoSmithKline PLC posted results Dec. 7 demonstrating activity against the omicron spike protein. Sotrovimab is the first monoclonal antibody showing preclinical efficacy against all COVID-19 variants, including the delta and omicron mutations, Vir CEO George Scangos said on a Dec. 7 call with analysts." Read more at the source #DrGPCR #GPCR #IndustryNews

Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation By stimulating human MRGPRD-expressing HeLa cells with the agonist β-alanine, we observed a release of

G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular effector proteins. Different agonists can promote differential receptor-induced signaling responses - termed bias - potentially by eliciting different levels of recruitment of effector proteins. As activation and recruitment of effector proteins might influence each other, thorough analysis of bias is difficult. Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well as arrestin3 binding to the muscarinic acetylcholine receptor M3 by utilizing FRET-based assays. In order to avoid interference between these interactions, we studied GRK2 binding in the presence of inhibitors of Gi and Gq proteins and analyzed arrestin3 binding to prestimulated M3 receptors to avoid differences in receptor phosphorylation influencing arrestin recruitment. We measured substantial differences in the agonist efficacies to induce M3R-arrestin3 versus M3R-GRK2 interaction. However, the rank order of the agonists for G protein- and GRK2-M3R interaction was the same, suggesting that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements for arrestin3 binding to M3R are distinct. Read full article

focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans

day commemorating the discovery of the DNA double helix structure in 1953 and the completion of the Human The completion of the Human Genome Project revealed that GPCR genes in the human genome range from approximately References National Human Genome Research Institute, U. S. (2002) National Human Genome Research Institute. The G-protein-coupled receptors in the human genome form five main families.

for their work on GPCR gene variants and human genetic disease Ilana Kotliar , Thomas Sakmar , et al. , Geoffrey Taghon , and Daniel Isom  for their research on Advances in yeast synthetic biology for human of airway smooth muscle GPCR Binders, Drugs, and more Expanding Structure-Activity Relationships of Human Artificial Intelligence Reviews, GPCRs, and more G protein-coupled receptor (GPCR) gene variants and human genetic disease Advances in yeast synthetic biology for human G protein-coupled receptor biology and

Scientific Data by Arne Hansen et a l has introduced a sensitive method for detecting GPCR mRNAs in human The study reports that human white blood cells express an average of 160 GPCR mRNAs, ranging from 123 Therefore this study significantly advances our understanding of GPCR expression in human immune cells

2022 "Neisseria meningitidis is a Gram-negative opportunistic pathogen that is responsible for causing human Human-associated bacteria encode a variety of bioactive small molecules with growing evidence for N-acyl However, only a small fraction of these metabolites has been identified from the human microbiota thus Here, we heterologously expressed an N-acyltransferase encoded in the obligate human pathogen N. meningitidis Both groups of metabolites suppress anti-inflammatory interleukin-10 signaling in human macrophage cell

Searching for antagonist activity, we performed systematic N-terminal truncations of human GLP-2(1-33 Experimental approach: COS-7 cells were transfected with the human GLP-2R and assessed for cAMP accumulation To examine selectivity, COS-7 cells expressing human GLP-1 or GIP receptors were assessed for cAMP accumulation

This review focuses on the vGPCRs encoded by the human β- and γ-herpesviruses. These include receptors from human cytomegalovirus, which encodes four vGPCRs: US27, US28, UL33, and UL78; human herpesvirus 6 and 7 with two receptors: U12 and U51; Epstein-Barr virus with one: BILF1;

Signaling A-Kinase-Anchoring-Protein Subtypes Differentially Regulate GPCR Signaling and Function in Human GPCRs GPCRs in Cardiology, Endocrinology, and Taste Regulator of G-protein signaling expression in human ligand recognition and G protein subtype selectivity of kisspeptin receptor Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy Structural analysis of the human C5a-C5aR1 complex

. for their work on Intracellular pathways of calcitonin gene-related peptide-induced relaxation of human Sexton et al. for their job on Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP muscarinic acetylcholine receptor-mediated calcium responses and the recruitment of β-arrestin in HSY human after internalization Intracellular pathways of calcitonin gene-related peptide-induced relaxation of human Function Molecular insights into G protein coupling specificity at a class A GPCR Cryo-EM Structure of the Human