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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

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

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.

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

engages its non-cognate ligand CD82 on hematopoietic stem cells (HSCs) to maintain their quiescence ( Hur The reported ACKR1 expression by macrophages in Hur et al. relied on using commercial anti-ACKR1 antibody

Zhang, H., et al., Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic

A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR Lior Peri ,   Donna Matzov ,  Dominic R Huxley ,   Peter Gmeiner ,  Peter J McCormick ,  Dorothee Weikert ,  Masha Y Niv ,  Moran Shalev-Benami , et al. recognition motifs for the MRGPRD GPCR A bitter anti-inflammatory drug binds at two distinct sites of a human

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

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

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

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,

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

September 2022 "Background Spinal cord injury (SCI) is a common trauma in clinical practices. Subacute SCI is mainly characterized by neuronal apoptosis, axonal demyelination, Wallerian degeneration, axonal remodeling, and glial scar formation. It has been discovered in recent years that inflammatory responses are particularly important in subacute SCI. However, the mechanisms mediating inflammation are not completely clear. Methods The gene expression profiles of GSE20907, GSE45006, and GSE45550 were downloaded from the GEO database. The models of the three gene expression profiles were all for SCI to the thoracic segment of the rat. The differentially expressed genes (DEGs) and weighted correlation network analysis (WGCNA) were performed using R software, and functional enrichment analysis and protein–protein interaction (PPI) network were performed using Metascape. Module analysis was performed using Cytoscape. Finally, the relative mRNA expression level of central genes was verified by RT-PCR." Read more at the source #DrGPCR #GPCR #IndustryNews

and more Isolation and functional identification of secretin family G-protein coupled receptor from Y-organ

Bitter Odorants and Odorous Bitters: Toxicity and Human TAS2R Targets. Transcriptomic analysis of human cytomegalovirus to survey the indirect effects on renal transplant recipients Pharmacological inhibition of neuropeptide Y receptors Y1 and Y5 reduces hypoxic breast cancer migration

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

Kelsey L Person , Abigail Alwin , Campbell Krusemark , Ezequiel Marron Fernandez de Velasco , Steven H

ligand binding, receptor activation, desensitization and trafficking is the apelin receptor (APJ) (Y.

Member Profile Antony Boucard Professor Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav What do you think is the next great hurdle in the aGPCR field? Alternative splicing events account for hundreds, if not thousands, of potentially divergent isoforms The diversity is humongous. why Mexican cuisine has obtained the coveted status of UNESCO ́s Intangible Cultural Heritage of Humanity

There are approximately 800 human GPCRs in the superfamily, controlling a broad range of physiological Selection of the libraries typically leads to the isolation of several hundred candidate hits, enriched of a small protein GPCR ligand using new peptide chemistry technology and rational design Gaertner, H. fully integrated PROcisionXᵀᴹ discovery platform Structure-based validation of Orion’s approach Zheng, Y. AIDS Res Hum Retroviruses, 37, 453-460. https://doi.org/10.1089/aid.2021.0010 · Successful first-in-human

highlights the importance of research work on the GPCR-mediated signal transduction garnered in the human Dopamine exerts its action in the human nervous system via dopamine receptors and human trace amine-associated These odorant receptors (ORs) now account for about 60% of all identified human GPCRs. George H. Edmond H.

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

Announces Positive Phase 3 Data for KINECT-HD Study Evaluating Valbenazine for Chorea Associated with Huntington Highly Statistically Significant Reduction in Chorea Movements (p < 0.0001) as Measured by the Unified Huntington's VMAT2) inhibitor being investigated as a once-daily treatment in adults with chorea associated with Huntington The study met the primary endpoint of reduction in severity of chorea, the cardinal motor feature in Huntington disease, as measured by change in the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal

large amounts of labelled training data comprising millions of parameters, becoming infeasible for a human ligands for dopamine receptors and adenosine receptors (He, Ben, Kuang, Wang & Kong, 2016; Kuang, Feng, Hu great potential, it is important to note that it is not a replacement for experimental validation and human

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

c-Jun N-terminal kinase Methods & Updates in GPCR Research Conserved pattern-based classification of human

Mutational Scanning for Enhanced Drug Discovery Cam Sinh Lu GPCR-BSD: a database of binding sites of human responses Structural and Molecular Insights into GPCR Function GPCR-BSD: a database of binding sites of human