Class B G protein-coupled receptors (GPCRs) are notoriously difficult to target by small molecules because Using the parathyroid hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination Here we found a key mechanical site that modulates the collective dynamics of the receptor and used this

October 2022 "G protein-coupled receptors (GPCRs) are important drug targets characterized by a canonical a wealth of GPCR structures that have been used in drug design and formed the basis for mechanistic activation impact of binding of agonists and antagonist/inverse agonists to selected structures of cannabinoid receptor 1 (CB1R), β2 adrenergic receptor (β2 AR) and A2A adenosine receptor (A2A AR). " Read more at the source

August 2022 "Abstract Sigma receptor is a transmembrane non-GPCR protein expressed mainly in the endoplasmic

October 2022 "Arrestins interact with G protein-coupled receptors (GPCRs) to stop G protein activation studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, but whether this process Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor (V2R) in complex with β-arrestin1. described GPCR-arrestin assemblies, associated with an original V2R/β-arrestin1 interface involving all receptor

October 2022 Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent in primary hepatocytes "A number of G protein-coupled receptors (GPCRs) are now thought to use endocytosis We tested if this is true for the glucagon receptor (GCGR), which mediates physiological regulation of epitope-tagged GCGRs undergo clathrin- and dynamin-dependent endocytosis in HEK293 and Huh-7-Lunet cells after activation We further show that endocytosis potentiates cytoplasmic cAMP elevation produced by GCGR activation and

The mouse cytomegalovirus G protein-coupled receptor homolog, M33, coordinates key features of in vivo receptors (GPCR). of distinct biochemical pathways activated by M33 is unknown. Identification of a MCMV M33 mutant (M33ΔC38) for which CREB signalling was disabled, but PLCβ activation IMPORTANCE G protein-coupled receptors (GPCRs) act as cell surface molecular "switches" which regulate

Opioid receptors are G-protein-coupled receptors (GPCRs) part of cell signaling paths of direct interest low pH at tissue targeted by opioid drugs in pain management could impact drug binding to the opioid receptor , because opioid drugs typically have a protonated amino group that contributes to receptor binding, In this review, we discuss the relationship between structure, function, and dynamics of opioid receptors from the perspective of the usefulness of computational studies to evaluate protonation-coupled opioid-receptor

October 2022 Cholesterol-Dependent Dynamics of the Serotonin1A Receptor Utilizing Single Particle Tracking : Analysis of Diffusion Modes "G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol Analysis of SPT trajectories revealed that relative populations of receptors undergoing various modes

September 2022 Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but Not G Protein Interaction "The calcium-sensing receptor is a homodimeric class C G protein-coupled ) unit that activates G protein-dependent signaling via twin Cysteine-rich domains linked to transmembrane severe hyperparathyroidism (NSHPT), receptor function was markedly impaired. We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors.

Obesity-induced changes in human islet G protein-coupled receptor expression: Implications for metabolic regulation G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that are

Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of a great variety

This question led Huang et al., 2022 to investigate the molecular basis involved in G protein-receptor , suggesting that the selectivity of the G-protein lies in intrinsic features of the receptor rather interactions are crucial for the coupling of G-proteins to serotonin receptors. residues of both G protein families, suggesting that receptors that activate both Gs and Gi/o do so by of class A GPCRs and potential therapeutic targets that are activated by the same endogenous ligand,

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors

Constitutive, Basal, and β-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor receptors (GPCRs) have emerged as key players in regulating (patho)physiological processes, including Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation Additionally, we investigated the constitutive (ligand-independent) and basal activity of MRGPRD and

G protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle production and circulation of vasoconstrictors, resulting in enhanced signalling through their cognate G protein-coupled receptors (GPCR). GPCR signalling through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) promotes VSMC proliferation In VSMC, G protein-coupled receptor kinase 2 (GRK2) is known to regulate numerous vasoconstrictor GPCRs

November 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed this work, molecular docking screens for allosteric modulators targeting the metabotropic glutamate receptor The mGlu5 receptor is activated by the main excitatory neurotransmitter of the nervous central system , L-glutamate, and mGlu5 receptor activity can be allosterically modulated by negative or positive allosteric The mGlu5 receptor is a promising target for the treatment of psychiatric and neurodegenerative diseases

Among the different families of G-protein-coupled receptors (GPCRs), adhesion GPCRs (aGPCRs) represent the selectivity of G-protein coupling using a mouse ADGRL3 receptor without extracellular region as Comparison between a predicted model of inactive receptor structure and self-activated Cryo-EM highlighted Overall the count of interactions between the last eight αH5 residues of each G protein with the receptor Boucard, A.A., Self-activated adhesion receptor proteins visualized.

August 2022 G protein-coupled receptor kinase type 2 and β-arrestin2: Key players in immune cell functions and inflammation "G protein-coupled receptor kinase type 2 (GRK2) and β-arrestin2 are representative proteins that regulate the transduction and trafficking of G protein-coupled receptor (GPCR) signaling The kinase GRK2 and the multifunctional scaffolding protein β-arrestin2 are key integrated signaling nodes in various biological processes, and both of them regulate cell proliferation and promote cell

September 2022 Fentanyl activates ovarian cancer and alleviates chemotherapy-induced toxicity via opioid receptor-dependent activation of EGFR "Background Fentanyl is an opioid analgesic and is widely used

September 2022 Computational study of the conformational ensemble of CX3C chemokine receptor 1 (CX3CR1 ) and its interactions with antagonist and agonist ligands "The CX3C chemokine receptor 1 (CX3CR1), a member of the class A of G Protein-Coupled Receptors (GPCR) superfamily, and its ligand fractalkine They participate in the activation, chemotaxis and recruitment of multiple immunological cells such as We analyzed the receptor conformational changes and described interactions within its key regions and

August 2022 "G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins."

September 2022 Lack of Oestrogen Receptor Expression in Breast Cancer Cells Does Not Correlate with Kisspeptin Signalling and Migration "Kisspeptin is an anti-metastatic mediator in many cancer types, acting through its receptor been associated with increased invasion and MMP-9 expression, leading to the suggestion that hormone receptor veracity of this claim, we compared endogenous KISS1R signalling and physiological output in the hormone receptor-negative MDA-MB-231 and BT-20 cell lines after KP-10 (shortest active kisspeptin peptide) stimulation.

coupling and mediate intracellular pathway bias "Within the intestine, the human G protein-coupled receptor assays in living cells to thoroughly profile both GPR35 isoforms for constitutive and ligand-induced activation and signaling of 10 different heterotrimeric G proteins, ligand-induced arrestin recruitment, and receptor Our results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates receptor-β-arrestin interaction.

September 2022 "G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes that regulate Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol Analysis of SPT trajectories revealed that relative populations of receptors undergoing various modes Notably, in cholesterol-depleted cells, we observed an increase in the confined population of the receptor

September 2022 "The human sweet taste receptor is a heterodimeric receptor composed of two distinct G-protein-coupled receptors (GPCRs), TAS1R2 and TAS1R3. revealed that the VFT, CRR and TMD of TAS1R3 interact with some sweeteners, including the sweet-tasting protein acid substitutions (D278A and E382A) known to abolish the response of the full-length TAS1R2/TAS1R3 receptor

August 2022 "Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors fluorescent ligands targeting the intracellular allosteric binding site (IABS) of the CC chemokine receptor

October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias receptor (GPCR) signaling. 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

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."