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β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living

2022 "As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand Here, we present two cryo-electron microscopy structures of CX3CR1-Gi1 complexes in ligand-free and CX3CL1

Together, these results link the morphogenetic effects of HH to the apico-basal distribution of SMO and

Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling,

cryo-ET) data on the ROS with structural knowledge on individual proteins to define the precise spatial limitations

It is activated by the three chemokine ligands CXCL9, CXCL10, and CXCL11 and enables the recruitment

Recurrent hypoglycemia increases hepatic gluconeogenesis without affecting glycogen metabolism or systemic lipolysis : To study the effects of RH on metabolic pathways associated with glucose counterregulation within liver their inhibitory regulators and downstream enzymes catalyzing glycogen metabolism, gluconeogenesis and lipolysis Additionally, we measured circulating FFA and glycerol to check lipolysis.

However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner.

from camelids, have become indispensable tools for interrogating GPCRs both in purified systems and in living

The structures reveal distinctive ligand engaging model and activation conformations of GPR110.

protein-coupled receptors (GPCRs) activation assumes that stimulation of heterotrimeric G protein signaling upon ligand

activated by these G protein-coupled receptors based on several factors, including the nature of the ligand These effects include reducing the atherosclerotic plaque area, improving the serum lipid profile, attenuation encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great importance to limit

binding location that raises many questions about the ligand interactions and stability, the binding site structure, and how all of these are affected by lipid molecules. Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound library enriched by weak donor groups for ligand search in such sites."

In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic

and promotes expression of phosphoenolpyruvate carboxykinase 1 (PCK1), the enzyme catalyzing the rate-limiting

We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a

analyses indicated that the palmitoylation of Go can allosterically stabilize the critical residues in the ligand-binding pocket of GPR97 and increase the affinity of the ligand for GPR97.

In rodents, intrathecal injection of its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC), causes time-dependent

However, most tools available to study the contribution of PKC isozymes have considerable limitations In this study, we generated and characterized human embryonic kidney 293A (HEK293A) cell lines devoid Our PKC KO cell lines expand the repertoire of KO HEK293A cell lines available to research GPCR pharmacology pharmacological tools to study PKC isozymes generally lack specificity and/or potency, we present the PKC KO cell lines

structures of B2R have provided molecular insights into the functions and regulation of B2R, which shed light

Chemical libraries containing fragment- (1.6 million molecules) and lead-like (4.6 million molecules) Among the top-ranked compounds, 59 fragments and 59 lead-like compounds were selected for experimental Of these, four fragment- and seven lead-like compounds were confirmed to bind to the allosteric site The results demonstrate that virtual screens of fragment- and lead-like chemical libraries have complementary

interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs.

assays were performed using PBMCs isolated from these individuals in response to the synthetic GPR15 ligand

Pc(4-4), a lead backbone cyclic peptide, was selected out of a mini-library, directed toward PAR2&4 PH-binding AYPGKF peptide ligand activation of PAR4 induces EGF receptor (EGFR) Tyr-phosphorylation, effectively

surgery is the cooperative improved action of the preproglucagon-derived hormones, glucagon, glucagon-like

highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand

the first receptors shown to transactivate other receptors: noticeably, these interactions are not limited

We also showed that the EMC promotes surface expression of C3aR, likely explaining its identification

presence of CaSR autoantibodies that operated as biased allosteric modulators of CaSR, and (g) were likely

A diverse pharmacopoeia of cannabinoid ligands is available, which has led to considerable advancements However, until recently, most CB2 ligands were highly lipophilic and as such not optimal for clinical A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties We review the current state of CB2 ligand development and progress in optimising physicochemical properties