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"Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled receptors The effect of pepducins at their cognate receptors has been shown to vary between antagonist, partial This review will focus in particular on pepducins designed from protease-activated receptors, C-X-C motif chemokine receptors, formyl peptide receptors, and the β2-adrenergic receptor. We will discuss the historic context of pepducin development for each receptor, as well as the structural

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 membranes and is believed to contribute to the segregated distribution of membrane constituents into domains Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol

Lipid molecules, such as phosphoinositides, can bind to specific domains of β-arrestins, promoting their membrane β-arrestin. β-arrestin reaches the receptor via lateral. Transient interaction with the receptor catalyzes β-arrestin activation, including β-arrestin inter-domain Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Molecular mechanism of b-arrestin-biased agonism at seven-transmembrane receptors. Annu. Rev.

Tracer concentration, receptor density, equilibrium assumptions, and ligand kinetics all influence whether curves correctly , recognizing G-protein coupling and kinetic effects rather than invoking multiple receptor Maria Majellaro, Johannes Broichhagen, and David Hodson discuss GLP-1 receptor probes, fluorescence-based

October 2022 "Arrestins interact with G protein-coupled receptors (GPCRs) to stop G protein activation Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor 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 We show that epitope-tagged GCGRs undergo clathrin- and dynamin-dependent endocytosis in HEK293 and Huh

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

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 When the same mutation was present in both VFT domains of receptor dimers, analogous to homozygous neonatal severe hyperparathyroidism (NSHPT), receptor function was markedly impaired. We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors.

August 2022 "As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide We revealed that AlphaFold2 could capture the overall backbone features of the receptors. structures were different in many aspects including the assembly of the extracellular and transmembrane domains

November 2022 "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various physiologies

November 2022 "Despite the growing number of G protein-coupled receptor (GPCR) structures, only 39 structures

subtype and a dominant negative form of Gs or Gi: 5-HT4, 5-HT6, and 5-HT7 with Gs, and 5-HT4 with Gi1 The binding pockets for serotonin were virtually identical between the receptor-Gs and receptor-Gi complexes The structural differences found between the receptor-Gs and receptor-Gi complexes evidenced that 5-HT4 These differences are mainly attributed to the characteristic Ras domain distance between Gs and Gi. Interestingly, in the case of promiscuous receptors they found that these receptors shared conserved

One such platform is the chemogenetic DREADD (designer receptor exclusively activated by designer drugs This study demonstrated Gαq-G-protein coupled receptor (GPCR)-mediated [Ca2+]i signaling involvement

(β2-AR), μ-opioid receptor (MOR), free fatty acid receptor 2 (FFA2R), and glucose-dependent insulinotropic polypeptide receptor (GIPR) (Figure 3). , and endosomal trafficking for the glucagon-like-peptide-1 receptor (GLP-1R), β2-adrenergic receptor (β2-AR), µ-opioid receptor (MOR), free fatty acid receptor 2 (FFA2R), and glucose-dependent insulinotropic Structural insights into G protein activation by D1 dopamine receptor.

G protein-coupled receptor signaling analysis using homogenous time-resolved Förster resonance energy This is moreso the case when detecting partial agonism or weak receptor interactions. , demonstrating high specificity and sensitivity in detecting ligand-receptor interactions.  A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery. A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.

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

Genome-wide identification of 216 G protein-coupled receptor (GPCR) genes from the marine water flea Diaphanosoma celebensis G protein-coupled receptors (GPCRs) are considered to have originated from early (Daphnia magna) reveals a high level of orthological relationship of amine, neuropeptide, and opsin receptor repertoire, while purinergic and chemokine receptors were highly differentiated in humans.

HEK293 cells reveals that both conventional and novel protein kinase C isozymes are involved in mGlu5a receptor internalization "The internalization of G protein-coupled receptors (GPCRs) can be regulated by PKC. to investigate the contribution of PKC isozymes in the internalization of the metabotropic glutamate receptor Direct activation of PKC and mutation of rat mGlu5a Ser901, a PKC-dependent phosphorylation site in the receptor C-tail, both showed that PKC isozymes facilitate approximately 40% of the receptor internalization.

Drug discovery often assumes receptor inhibition follows simple rules—agonist binds, antagonist blocks Ways Schild plots reveal hidden complexities like allosterism and receptor heterogeneity. No reduction  in the maximal response (the receptor can still be fully activated). Curvature  can signify heterogeneous receptors  or mixed response mechanisms. In practice, a deviation in slope or curvature isn’t noise—it’s the receptor speaking.

August 2022 A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer "Adhesion G protein-coupled receptors (adhesion GPCRs), as a member of the G protein-coupled receptors (GPCRs) superfamily, have gradually entered the field of vision of

cryogenic-electron microscopy (cryo-EM) is used extensively to determine structures of activated G protein-coupled receptors However, applying it to GPCRs without signaling proteins remains challenging because most receptors lack structural features in their soluble domains to facilitate image alignment. exploring different fusion protein designs, which lead to structures of antagonist bound A2A adenosine receptor

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 In this work we present the study of the CX3CR1 receptor employing extensive atomistic Molecular Dynamics We analyzed the receptor conformational changes and described interactions within its key regions and

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 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 receptor-B2 (MRGPRB2), plays important roles in immune response.

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

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

August 2022 "G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and

The Problem: Hundreds of Receptors, Almost No Ligands Alessandro’s work focuses on olfactory GPCRs—nearly 400 distinct receptors that play key roles in smell but remain largely uncharacterized . Enter AlphaFold: Predicting the “Face” of a Receptor When Alessandro began his PhD, structural models “When they released the first structure of the odorant receptors… AlphaFold already had it, without any From Prediction to Discovery One of Alessandro’s projects focused on receptor R5VK1 , where his team

identified 30 N-acyl amides with representative members serving as agonists of the G-protein coupled receptor

The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms