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follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled

Single nucleotide polymorphisms (SNPs) in the Adhesion G Protein-Coupled Receptor L3 (ADGRL3) gene are However, the effect of ADGRL3 non-synonymous SNPs (nsSNPs) on the ADGRL3 protein function is vastly unknown

October 2022 Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected to inverse agonism "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various physiologies. 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 inverse agonism. Using a co-immunoimmobilization assay, we found that transient β2-AR dimers exist in a resting state, and the dimer was disrupted by the inverse agonists. A Gαs preferentially interacts with dimeric β2-AR, but not monomeric β2-AR, in a resting state, resulting in the production of a resting cAMP level. The formation of β2-AR dimers requires cholesterol on the plasma membrane. The cholesterol did not interfere with the agonist-induced activation of monomeric β2-AR, unlike the inverse agonists, implying that the cholesterol is a specific factor regulating the dimerization of β2-AR. Our model not only shows the function of dimeric β2-AR but also provides a molecular insight into the mechanism of the inverse agonism of β2-AR." Read more at the source #DrGPCR #GPCR #IndustryNews Subscribe to the Dr. GPCR Newsletter

multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened "The oncogenic G-protein-coupled This effect involves the sequential and additive action of protein kinase A, casein kinase I, and the

Herein, we identified GPR108, a GPCR protein described in innate immune system, is a potential therapeutic

October 2022 "Type 2 bradykinin receptor (B2R) is an essential G protein-coupled receptor (GPCR) that

receptor-transducer coupling and mediate intracellular pathway bias "Within the intestine, the human G protein-coupled isoforms for constitutive and ligand-induced activation and signaling of 10 different heterotrimeric G proteins Our results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates

The hepatitis B virus X protein (HBx) is involved in the process of hepatocellular carcinoma via the ARRB1 interacted with HBx, and the autophagic core protein MAP1LC3/LC3, a scaffolding protein, was essential HCC.Abbreviations: ARRB1: arrestin beta 1; ACTB: actin beta; AMPK: adenosine monophosphate (AMP)-activated protein immunohistochemistry; JAK1: Janus kinase 1; LOX: lysyl oxidase; MAP1LC3B/LC3: microtubule associated protein marker of proliferation Ki-67; MTOR: mechanistic target of rapamycin kinase; MAPK: mitogen-activated protein

Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled

One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled

regulation of cancer cell cycle and metastasis "β-Arrestins are ubiquitously expressed intracellular proteins now recognized that in addition to GPCR arresting (hence the name arrestin). β-Arrestins are adaptor proteins recruitment, activation, and scaffolding of numerous cytoplasmic signaling complexes and assist in G-protein

October 2022 "G protein-coupled receptors (GPCRs) play critical roles in human physiology and are one

Meanwhile, cGAS deletion upregulated profibrotic Yes-associated protein (YAP) signaling in endothelial Pharmacological targeting of cGAS/STING-YAP signaling by both a small-molecule STING agonist, SR-717, and a G protein-coupled

Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and their G protein-coupled Neuropeptides and their specific receptors (primarily G protein-coupled receptors, GPCRs) regulate multiple

October 2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric modulation in angiotensin receptors: IUPHAR Review 34 "Functional advances have guided our knowledge of physiological and fatal pathological mechanisms of the hormone angiotensin II (AngII) and its antagonists. Such studies revealed that 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. Recently, X-ray structures of both AngII receptors (AT1 and AT2 receptors) bound to peptide and non-peptide ligands have been elucidated, providing new opportunities to examine the dynamic fluxes in the 3D architecture of the receptors, as the basis of ligand selectivity, efficacy, and regulation of the molecular functions of the receptors. Constituent structural motifs cooperatively transform ligand selectivity into specific functions, thus conceptualizing the primacy of the 3D structure over individual motifs of receptors. This review covers the new data elucidating the structural dynamics of AngII receptors and how structural knowledge can be transformative in understanding the mechanisms underlying the physiology of AngII." Read more at the source #DrGPCR #GPCR #IndustryNews

Mutations in G protein-coupled receptors (GPCRs) underlie numerous diseases.

October 2022 "Psychedelics, also known as classical hallucinogens, affect processes related to perception, cognition and sensory processing mostly via the serotonin 5-HT2A receptor (5-HT2AR). This class of psychoactive substances, which includes lysergic acid diethylamide (LSD), psilocybin, mescaline and the substituted amphetamine 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), is receiving renewed attention for their potential therapeutic properties as it relates to psychiatric conditions such as depression and substance use disorders. Current studies focused on the potentially clinical effects of psychedelics on human subjects tend to exclude sex as a biological variable. Much of the understanding of psychedelic pharmacology is derived from rodent models, but most of this preclinical research has only focused on male mice. Here we tested the effects of DOI on head-twitch behavior (HTR) - a mouse behavioral proxy of human psychedelic potential - in male and female mice. DOI elicited more HTR in female as compared to male C57BL/6J mice, a sex-specific exacerbated behavior that was not observed in 129S6/SvEv animals. Volinanserin (or M100907) - a 5-HT2AR antagonist - fully prevented DOI-induced HTR in male and female C57BL/6J mice. Accumulation of inositol monophosphate (IP1) in the frontal cortex upon DOI administration showed no sex-related effect in C57BL/6J mice. However, the pharmacokinetic properties of DOI differed among sexes - brain and plasma concentrations of DOI were lower 30 and 60 min after drug administration in female as compared to male C57BL/6J mice. Together, these results suggest strain-dependent and sex-related differences in the behavioral and pharmacokinetic profiles of the 5-HT2AR agonist DOI in C57BL/6J mice, and support the importance of studying sex as a biological variable in preclinical psychedelic research." Read more at the source #DrGPCR #GPCR #IndustryNews

intracellular domain dictate and condition long-term GPCR activities associated with the regulation of protein understanding of this function of GPCRs is likely to significantly augment our ability to further employ these proteins

G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular effector proteins. As activation and recruitment of effector proteins might influence each other, thorough analysis of bias Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements

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 receptor (GPCR) senses extracellular Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT) unit that activates G protein-dependent

August 2022 "The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans." Read more at the source #DrGPCR #GPCR #IndustryNews

G protein-coupled receptors (GPCRs) are a vast family of membrane-bound proteins crucial for transmitting avoiding interactions with non-cognate G proteins [1]. Gq proteins could bolster Gs dependent-β2-adrenergic receptor-mediated cAMP signalling, while Gs proteins prepare the GPCR in a manner that optimizes subsequent cognate G protein activation. landscape where non-cognate G proteins play a critical preparatory role.

Human cells express over 800 G-protein-coupled receptors (GPCRs) to facilitate communication with the Capturing the dynamics of GPCR activation has always been a challenge because G protein activation in Concurrently, the α1 helix extends, propagating structural changes throughout the G protein. Physiological roles of G protein-coupled receptor kinases and arrestins. Time-resolved cryo-EM of G-protein activation by a GPCR. Nature (2024).

G protein-coupled receptors (GPCRs) are integral membrane proteins crucial for sensing extracellular Resonance Energy Transfer (BRET), has revolutionized the study of GPCRs by enabling real-time monitoring of protein-protein and a G protein detector tagged with an Nluc donor. Wan, Q., et al., Mini G protein probes for active G protein-coupled receptors (GPCRs) in live cells.  Eidne, Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein

can identify essential domains and residues crucial for the protein's biological function. Additionally, DMS is not universally applicable to all proteins; it struggles with proteins that lack Deep mutational scanning: assessing protein function on a massive scale. Measuring the activity of protein variants on a large scale using deep mutational scanning. Molecular basis of proton-sensing by G protein-coupled receptors.

One fascinating aspect of the cellular signaling network is the crosstalk between G protein-coupled receptors involvement in a myriad of physiological processes, mediate mostly signaling through heterotrimeric G proteins The researchers focused on the phosphorylation of the G protein subunit Gαi at specific residues within The ability of growth factors to modulate G protein signaling through specific phosphorylation events For instance, the sequestration of G proteins from canonical GPCR-dependent pathways by growth factor

CXV: The Class F of G Protein-Coupled Receptors Yusman Manchanda, Dr. Alejandra Tomas, et al. for their research on Engineered mini-G proteins block the internalization of Jianming Han, Tao Che for their analysis of GPCR-G protein selectivity revealed by structural pharmacology receptor drug discovery The application of targeted protein degradation technologies to G protein-coupled receptors Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics

This Week’s Highlights: G protein-coupled receptor (GPCR) pharmacogenomics Miles D Thompson , David Deupi , Yang Du , Brian K Kobilka Red and far-red cleavable fluorescent dyes for self-labelling enzyme protein Joshua Levitz , Ben Jones , Johannes Broichhagen Design of allosteric modulators that change GPCR G protein Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein of antibodies, which recognized native receptor Design of allosteric modulators that change GPCR G protein