However, the function of dimeric β2-AR is still elusive. Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating A Gαs preferentially interacts with dimeric β2-AR, but not monomeric β2-AR, in a resting state, resulting The formation of β2-AR dimers requires cholesterol on the plasma membrane. mechanism of the inverse agonism of β2-AR."

However, the function of dimeric β2-AR is still elusive. Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating A Gαs preferentially interacts with dimeric β2-AR, but not monomeric β2-AR, in a resting state, resulting The formation of β2-AR dimers requires cholesterol on the plasma membrane. mechanism of the inverse agonism of β2-AR."

August 2022 "Abstract The β3 -adrenergic receptor (β3 -AR) is found in several tissues such as adipose Two β3 -AR agonists are used clinically: mirabegron 1 and vibegron 2, which are indicated for overactive Hence, new β3 -AR agonists are needed as starting points for drug development. Previous pharmacophore modeling studies of the β3 -AR did not involve experimental in vitro validation 8 compounds were active in CHO-K1 cells expressing the mouse β3 -AR."

We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and a partial agonist or a very weak partial agonist, and compare them to the β1-AR-Gs structure in complex Cellular functional studies with mutations of β1-AR residues show effects on the cellular signaling from β1-AR to the cAMP response initiated by the three different ligands, with residue-specific functional Biochemical investigations uncover that the intermediate state complex comprising β1-AR and nucleotide-free

emerging prognostic indicator and future therapeutic target " Purpose: Beta 2-Adrenergic Receptor (β2-AR However, the role of β2-AR in oral cancer is not well identified. The present study aimed at investigating the β2-AR gene expression and its significance in relation with Immunohistochemistry, western blot and quantitative real-time PCR techniques were used to analyze β2-AR

receptors (GPCRs) are important drug targets characterized by a canonical seven transmembrane (TM) helix architecture 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 #DrGPCR #GPCR #IndustryNews

indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR

August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence

August 2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer cell cycle and metastasis "β-Arrestins are ubiquitously expressed intracellular proteins with many functions However, current investigations have now recognized that in addition to GPCR arresting (hence the name arrestin). β-Arrestins are adaptor proteins that control the recruitment, activation, and scaffolding processes which underlie the mechanism of β-arrestins in the onset of cancer.

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 The kinase GRK2 and the multifunctional scaffolding protein β-arrestin2 are key integrated signaling GRK2/β-arrestin2 play multiple roles in the pathological mechanisms of a wide range of diseases including implications of GRK2/β-arrestin2 in various inflammatory diseases."

August 2022 GRK2 selectively attenuates the neutrophil NADPH-oxidase response triggered by β-arrestin

Although studies have focused on the G-protein signaling state, the mechanism for β-arrestin signaling in response to biased ligands and could therefore participate in a molecular mechanism to trigger β-arrestin

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent vs. β-arrestin Although this field has exploded during the past two decades, it is only recently that highly β-arrestin now summarize important pharmacological, molecular, and cellular studies relevant to D1-mediated β-arrestin-related emerged from behavioral and physiological studies implying that bias toward or against D1-mediated β-arrestin

September 2022 " Background and purpose: The interaction of arrestins with G-protein coupled receptors GPCRs that internalize without arrestin have been classified as "class A" GPCRs whereas "class B" GPCRs co-internalize with arrestin into endosomes. The interaction of arrestins with GPCRs requires both agonist activation and receptor phosphorylation question whether agonists with very slow off-rates can cause the formation of particularly stable receptor-arrestin

Our previous study indicated that ARBB1 (arrestin beta 1) promotes hepatocellular carcinogenesis (HCC However, the role of ARRB1 in HBx-related HCC remains unclear. Herein, we identified that ARRB1 was upregulated by HBx in vivo and in vitro. Abbreviations: ARRB1: arrestin beta 1; ACTB: actin beta; AMPK: adenosine monophosphate (AMP)-activated Read full article

Arrestins regulate a wide range of signaling events, most notably when bound to active G protein-coupled Among the known effectors recruited by GPCR-bound arrestins are Src family kinases, which regulate cellular Here, we focus on arrestin-3 interactions with Fgr kinase, a member of the Src family. and arrestin-independent pathways. Read full article

The hypothesis arises that GPCR and β-arrestin-centered effector complexes vary based on subcellular GPCR–β-Arrestin complexes: versatile scaffolding platforms β-arrestins exhibit interactions with over 100 diverse proteins, presenting an array of effectors that could be recruited to GPCR–β-arrestin complexes and prevalence of GPCR–β-arrestin–effector complexes. However, β-arrestins do not consistently act as oncogenes or tumor suppressors.

. β-arrestin reaches the receptor via lateral. Transient interaction with the receptor catalyzes β-arrestin activation, including β-arrestin inter-domain between β-arrestin and the receptor. Membrane phosphoinositides regulate GPCR-β-arrestin complex assembly and dynamics. Molecular mechanism of GPCR-mediated arrestin activation.

Artificial intelligence - Machine learning vs Deep Learning GPCRs have long been recognized as important Machine learning (ML) and deep learning (DL) are subfields of artificial intelligence (AI) that involve While they share similarities, there are notable differences in respect to neural network architecture The future According to the authors, the future of AI relies in 6 main areas: 1. Check the original article at https://pubmed.ncbi.nlm.nih.gov/37161878/ #GPCR #DrGPCR #Ecosystem

With around 187 people dying every day from an opioid overdose in the U.S., combatting the opioid overdose minimally recruit β-arrestin 2 to MORs may also cause opioid side effects2. MOR and was modified through CRISPR/Cas9 to knock out β-arrestin 1 and 2 gene expression. activation of the β-arrestin pathway under Gi/o activation-MOR, being crucial the formation of β-arrestin and reinforce the role of β-arrestins in the physiological opioid system.

November 2022 Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer cell cycle and metastasis "β-Arrestins are ubiquitously expressed intracellular proteins with many functions However, current investigations have now recognized that in addition to GPCR arresting (hence the name arrestin). β-Arrestins are adaptor proteins that control the recruitment, activation, and scaffolding processes which underlie the mechanism of β-arrestins in the onset of cancer.

October 2022 β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells "β-arrestins mediate regulatory processes for over 800 different G However, whether β-arrestin1 and 2 respond differently for binding to the same GPCR is still unknown. Employing GRK knockout cells and β-arrestins lacking the finger-loop-region, we show that the two isoforms Moreover, we assess β-arrestin conformational changes that are induced specifically by proximal and distal

October 2022 Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias

October 2022 "Arrestins interact with G protein-coupled receptors (GPCRs) to stop G protein activation Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor (V2R) in complex with β-arrestin1. It reveals an atypical position of β-arrestin1 compared to previously described GPCR-arrestin assemblies

September 2022 Exploiting Dependence of Castration-Resistant Prostate Cancer on the Arginine Vasopressin We previously demonstrated that the G protein-coupled receptor (GPCR) arginine vasopressin receptor type1A AVPR1A is part of a family of GPCR's including arginine vasopressin receptor type 2 (AVPR2). Furthermore, we found that castration-resistant cells produced AVP, the endogenous ligand for arginine These data indicate that the AVP/arginine vasopressin receptor signaling axis represents a promising

September 2022 "MRAP2 is a small simple transmembrane protein arranged in a double antiparallel topology The aim of this work was to analyze the functional role of the specific arginine residue at position R125H and R125C, which are found in human patients with extreme obesity, and mouse MRAP2, in which arginine

β-arrestins (βarrs) play multifaceted roles in the function of G protein-coupled receptors (GPCRs). βarrs Read full article

GPCRs share a common mechanism of action via the β-arrestin scaffolding signaling complexes, which not tau but also show that β-arrestin1 levels are increased in brains of Frontotemporal lobar degeneration Increased β-arrestin1 in turn drives the accumulation of pathogenic tau, whereas reduced ARRB1 alleviates Biochemical and cellular studies show that β-arrestin1 drives tauopathy by destabilizing microtubules Read full article