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GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states Fan Liu , Han Zhou , Xiaonong Li , Liangliang Zhou , Chungong Yu , Haicang Zhang , Dongbo Bu 🤩 Seriously, why GPCR Events to keep you informed and engaged GPCR Jobs connecting candidates with positions Direct line This strategic decision to limit free content is essential as we need to increase revenue to support

assay and Kd= 42nM in Tag-lite®). Competition experiments of binding of fluorescent ligand CELT-335 to living HEK-293 T cells expressing W.; Wu, Y.; Zhao, S.; Shui, W.; Li, S.; Korde, A.; Laprairie, R. B.; Stahl, E. L.; Ho, J. Cell   2016 , 167  (3), 750-762.e14. https://doi.org/10.1016/j.cell.2016.10.004 . (5)         Li, X.; A Fluorescent Ligand-Binding Alternative Using Tag-Lite® Technology.

Live-cell high-content screening (HCS) offers an increasingly valuable alternative. By quantifying ligand–receptor interactions directly in intact cells, HCS allows researchers to observe Using HEK-293 cells stably expressing CB2R, fluorescent tracers such as CELT-331 can report on ligand HCS can support CB2 ligand discovery: 1. CB2 ligand characterization.

GPCR-focused programs, the ability to visualize receptor localization, internalization kinetics, and ligand Yet, despite remarkable progress, HCS workflows remain vulnerable to several performance-limiting factors How Fluorescent Ligands Strengthen HCS Assays: The Case of CELT-331 Fluorescent ligands are now considered Their ability to visualize ligand–receptor interactions directly in living cells produces data that are information that clarifies receptor behavior under different ligand conditions.

The donors used in this technique have longer half-lives  than other fluorophores (between 300μs–1 ms The donors act as light-harvesting antennas, capturing light from all directions, unlike the dipole-dipole This also improves detection of low affinity or slow binding ligands. A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery. A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.

Fluorescent ligands based on small molecules bind to the functional sites of receptors in live cells, Using Fluorescent Ligands Over Antibodies in Flow Cytometry Assays: Key Advantages These are key limitations Compatibility with live cells No need for fixation of permeabilization. many limitations of the antibody-based methods. Illuminating the life of GPCRs.

October 2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric tissue response to a given dose of the hormone or its antagonist depends on receptors that engage the ligand Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. , X-ray structures of both AngII receptors (AT1 and AT2 receptors) bound to peptide and non-peptide ligands Constituent structural motifs cooperatively transform ligand selectivity into specific functions, thus

Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH

October 2022 Mechanism of enhanced sensitivity of mutated β-adrenergic-like octopamine receptor to amitraz Previous assays verified that a typical G protein-coupled receptor, β-adrenergic-like octopamine receptor

Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric These forms were stabilized differently by distinct ligands. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties

less side effects, and tools to explore the ORs nature and function, various (poly)pharmacological ligand That is, besides classical ligands, a great number of bivalent ligands (i. e. aiming on two distinct OR subtypes), univalent heteromer-selective ligands and bitopic and allosteric ligands have been synthesized The scope of our review is to present the most important of the aforementioned ligands, highlight their

September 2022 Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs have been associated with various cancers, with some members of the RGS family being associated with liver significantly associated with some tumor-related signaling pathways and long intergenic non-coding RNAs (lincRNAs : LINC00511, PVT1, MIR4435-2HG, BCYRN1, and MAPKAPK5-AS1) that exhibit oncogenic potential. Taken together, we showed that RGS20 correlates with a few HCC-associated lincRNAs harboring oncogenic

Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH

Applications of Fluorescent Probes in Confocal Imaging of GPCRs: From Live to Fixed Cells GPCRs are present A High Content Screening focused microscope that has a confocal-like mode as well. The biological context (live or fixed cells), the spatial temporal resolution and other experimental Figure 2.Left panel, confocal microscopy of living cells incubated for 1h at 37ºC with CELT-327. A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.

Straight Lines, Slopes, and Systems Not all data bends into curves. Sometimes you’re working with linear fits: Schild plots, dose ratios, regression models. What used to be a gray area— “maybe these lines are different?” Does Your Assay Agree With the Literature? Your experiment gives a pKB of 8.0. The literature says 7.5. Is that consistent, or is your assay biased?

Understanding receptor-ligand interaction is key in drug discovery and biomedical research. ligands’ interaction with the receptor. General structure of a fluorescent ligand. Live-cell imaging:  Fluorescent ligands can be used to study cellular and tissue location of a receptor Fluorescent ligands: Bringing light to emerging GPCR paradigms.

The dysfunction of these receptors has been linked to the development of many serious pathologies, like binding experiments in live cells. Since BBVs lack downstream signaling, doing a quantitative lice-cell assay using the same ligand would Inhibition of CELT-419 binding to live HEK-D3R cells by dopaminergic receptor ligands. The use of CELT-419 as a fluorescent ligand is not limited by the methods used in this study.

Today, we're thrilled to announce that Terry's Corner is officially live !   GPCR Premium Members a significantly reduced access  to Terry's Corner for a limited time.  

Discover how receptors actually behave, how ligands uniquely sculpt their function, and how cryptic allosteric

interact with molecular targets involved in disease pathways is where the development of new therapeutics lies bound to protein rotates slower than a free fluorescent ligand. ligand is bound to the protein. When polarized light hits a free fluorescent ligand, its rotation speed is so fast that the emission On the other hand, when the polarized light hits the bound fluorescent ligand, the slower rotation speed

What do roasted ox liver and AI-powered virtual screening have in common? It’s one of the earliest medical texts, prescribing liver to treat night blindness. Fast-forward a few thousand years, and we’re talking beta receptors, receptor theory, and AI-generated ligands

Think of it like catching a train: two passengers have tickets (affinity), but only the one who sprints When Equilibrium Lies Sometimes, numbers don’t add up. It’s like calculating a runner’s pace and realizing they’d have to break the sound barrier to make the It’s like waiting for popcorn: at first, nothing happens, then suddenly the bag explodes with pops. The reality is dynamic—ligands arrive, depart, and interact in ways that standard assays often miss.

The real friction point lies downstream : translating receptor–ligand interactions into actionable development well-behaved molecule in a dish can fail spectacularly in vivo, leaving teams with years of sunk costs and little Real systems don’t live at equilibrium. Allosteric modulators and biased ligands aren’t exotic outliers—they’re increasingly common outcomes A growing on-demand library  where enzyme inhibition, activation, and metabolism are demystified with

That simple ask pulled a young chemist out of the fume hood and into the messy, electrifying world of live-cell He was a PhD student studying ion channels — living in a world defined by reaction mechanisms, synthetic Instead of round-bottom flasks, he was looking at living cells under a confocal microscope. the receptor across islets, tissue slices, and ultimately living animals. Collaboration as the Driver Behind Today’s GPCR Imaging Breakthroughs Behind the technical success lies

including receiving the British Pharmacological Society Vane Medal and switching on the Christmas lights Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory Indeed, all the details below will be limited to Premium Members . Biologist GPCR Activation and Signaling Activation of the proton-sensing GPCR, GPR65 on fibroblast-like

However, these conventional assays often provide limited information on intermediate signaling events These biosensors have facilitated the investigation of various aspects of GPCR signaling, including ligand Moreover, these experiments can be conducted in live cells, preserving the physiological context and BERKY consists of a membrane linker, a BRET donor, an ER/K α-helix linker, a BRET acceptor, and an active Galés, C., et al., Real-time monitoring of receptor and G-protein interactions in living cells. 

GPCRs are present in a range of conformations, and the binding of a ligand, as well as interactions with signaling molecules like G proteins, can selectively stabilize specific conformations (Gether 2000). GPCR ligands pharmacology The impact of a ligand on a receptor's structure and biophysical attributes , and consequently on the biological response, is referred to as ligand efficacy. selectively activate specific cellular outcomes linked to that GPCR.

The method has found druggable sites overlapping with the cocrystallized allosteric ligands in 21 GPCR Results show that for each of the 21 structures with bound ligands there exist many other GPCRs that However, ligands binding at the same location generally show little or no similarity, and the amino acid residues interacting with these ligands also differ. binding sites among the limited number of potential locations."

Limited evidence has been reported on the impact of cannabis or its components, delta-9-tetrahydrocannabinol accumulation, and gene and protein expression of major milk protein and lipid synthesizing markers. We hypothesized that THC and CBD will negatively impact the synthesis of milk proteins and lipids, as well as lipid markers in HC11 cells. Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP), lipid

The answer lies in a misunderstood property called efficacy—the power of a drug to trigger a response