protein-coupled receptors (GPCRs) play critical roles in human physiology and are one of the prime targets for marketed development of ligands targeting the binding site of endogenous ligands (orthosteric site), allosteric modulators Recent advances in the structure determination of GPCRs bound to different types of allosteric modulators have led to the identification of multiple allosteric sites and significantly enhanced our understanding Read more at the source #DrGPCR #GPCR #IndustryNews

TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. Read more at the source #DrGPCR #GPCR #IndustryNews

as the most important drug targets. However, many studies over the past decade have reported that internalized membrane receptors can trigger of physiology/pathology and novel drug targets for precision medicine. of GPCR signaling and novel drug targets for precision medicine." Read more at the source #DrGPCR #GPCR #IndustryNews

C-X-C motif chemokine receptor 4 (CXCR4), a G-protein-coupled receptor (GPCR), has one identified natural initiates several intracellular signaling pathways, regulating cell proliferation, survival, chemotaxis, migration , angiogenesis, adhesion, as well as bone marrow (BM)-resident cells homing and mobilization. Additionally, CXCR4 is expressed by tumor cells in blood malignancies and solid tumors." Read more at the source #DrGPCR #GPCR #IndustryNews

Studies of GPR21 knock-out mice indicated that GPR21 may be involved in promoting macrophage migration THP-1 cells were activated and differentiated into either M1 or M2 macrophages. Cell migration was detected by the Boyden chamber migration assay, performed on macrophages derived from both the THP-1 cell line and human peripheral blood monocytes." Read more at the source #DrGPCR #GPCR #IndustryNews

Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor We used TIRF microscopy and a statistical method to track and classify the motion of different receptor cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. " Read more

form of Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia, is due to mutations in the ANOS1 gene that encodes for the extracellular matrix (ECM) protein anosmin 1. In the current report we present evidence of the modulation of PK2/PKR2 activity by anosmin 1, since pull-down (glutathione-S-transferase) and analysis of the N267K mutation in the fibronectin type III Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Melanocortin 4 receptor (MC4R) is part of the leptin-melanocortin pathway and plays an essential role in mediating energy homeostasis. Mutations in the MC4R are the most frequent monogenic cause for obesity. of setmelanotide signaling at wild-type MC4R (MC4R-WT). Read more at the source #DrGPCR #GPCR #IndustryNews

It plays a key role in the regulation of human calcium and thus mineral metabolism. Transfected HEK-293 cells were assessed for Ca2+o -stimulated Ca2+i mobilization using mutations in either Mutant heterodimers containing one wild-type (WT) and one mutant VFT domain, however, corresponding to We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors. for Bone and Mineral Research (ASBMR)."

activation in macrophages "The putative medium-chain free fatty acid receptor GPR84 is a G protein-coupled , monocytes, and macrophages in the periphery and microglia in the brain. Infiltrating GPR84+ macrophages are significantly increased in the colonic mucosa of both the UC patients and the mice with colitis. activation, while the loss of GPR84 prevents the M1 polarization and properties of proinflammatory macrophages

September 2022 To probe the activation mechanism of the Delta opioid receptor by an agonist ADL5859 started pharmaceutical target for pain management. In this study, a DOR agonist ADL5859 was docked to the inactive DOR and multiple microsecond molecular dynamic (MD) simulations were conducted to probe the activation mechanism. Read more at the source #DrGPCR #GPCR #IndustryNews

We have carried out MARTINI coarse-grained molecular dynamics simulations of SMO in POPC and in ciliary membrane models, respectively, to study the interactions of SMO with cholesterol and other lipid molecules in the ciliary membrane, and to gain molecular-level insights into the role of the primary cilia in cholesterol-binding motifs. Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways subtype of TNBC ( P  = 0.001), total metastatic events ( P  = 0.019) and liver metastasis ( P  = 0.011 At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing Read more at the source #DrGPCR #GPCR #IndustryNews

FSHR is involved in reproductive processes such as gonadal development and maturation. We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data with molecular modeling to generate experimentally driven full-length models. These models provide insights into the interface, important side-chain interactions, and activation mechanism Read more at the source #DrGPCR #GPCR #IndustryNews

Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on the skeletal metabolism , but results of human studies mainly conducted in females are controversial. The present study aims to investigate the possible role of FSH excess in male bone health, by comparing Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 PLC-IP3-ORAI pathway participates in the activation of the MRGPRB2 receptor in mouse peritoneal mast cells "A novel mast cell-specific G-protein-coupled receptor (GPCR), known as Mas-related G protein-coupled However, the opening of ion channels mediated by MRGPRB2 activation remains unclear. Our results indicated the involvement of the PLC-IP3-ORAI signaling pathway and CACCS in MRGPRB2-mediated mast cell activation."

Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL focusing on macrophage IL‐1β production in ECRS pathogenesis. Methods We investigated the therapeutic effects of trehalose and saccharin on macrophage IL‐1β production and eosinophilia in the mouse model of ECRS with myeloid cell‐specific autophagy‐related gene 7 ( Atg7 Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Lysine 101 in the CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal proteins that transduce signals across the plasma membrane and orchestrate a multitude of physiological We have previously shown, using a combination of experimental and simulation approaches, that membrane receptor imparted by cholesterol, independent of membrane cholesterol content. Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "G protein‐coupled receptors (GPCRs) are valuable therapeutic targets for many diseases We used machine learning (ML) techniques to identify specific interactions that correlate with the agonist We demonstrate with the application of ML methods that it is possible to identify the key interactions Meanwhile, the antagonist ligands made interactions with W2866.48×48 and Y3167.43×42, both residues considered Read more at the source #DrGPCR #GPCR #IndustryNews

within myotubes and tissues of skeletal muscle from both murines and humans, thus representing a potentially Murine L6 skeletal muscle cells were used in order to clarify additional possible molecular signaling In conclusion, in skeletal muscle, CB1 receptors were recognized to be important moderators of NR4A1 and NR4A3 mRNA gene expression; these actions may have possible clinical benefits. Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor (MOR), whereas naloxone, with only slight structural changes compared to morphine, The mechanism by which the MOR distinguishes between the two is unclear. Molecular dynamics (MD) simulations on a 1-μs time scale and metadynamics-enhanced conformational sampling EM-1 in activating MOR.

September 2022 Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism , microbiota, and T cell-induced inflammation "Gut intraepithelial lymphocytes (IELs) are thought to proximal T cell receptor signaling in a protein-kinase-A-dependent manner. activation in gut IELs to modulation of microbiota composition and control of intestinal and systemic Read more at the source #DrGPCR #GPCR #IndustryNews

on the plasma membrane. Results obtained with the MRAP2 mutants R125H and R125C, which are found in human patients with extreme obesity, and mouse MRAP2, in which arginine 125 is normally replaced by histidine, were compared with those obtained with human MRAP2. of the MRAP2-PKR2 complex."

GPR15 signals through the Gi/o pathway to decrease intracellular cyclic adenosine 3',5'-monophosphate Moreover, whether the receptor can also couple to Gs , Gq/11 and G12/13 is unclear. 25-81) and 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 Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Metabotropic γ-aminobutyric acid receptor (GABABR), a class C G protein-coupled receptor G protein (GP) binding mode. Here, we use molecular metadynamics computations to predict the mechanism by which the inactive GP induces This mechanism provides fresh insights into the mechanistic details of class C GPCRs activation expected Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant of CCR9 expression and tumor progression-associated markers in SACC. mice following CCL25, Vercirnon and LY294002 treatment." Read more at the source #DrGPCR #GPCR #IndustryNews