Search Results
397 items found for "proteomics"
- Single-molecule counting applied to the study of GPCR oligomerization
counting techniques enable a precise determination of the intracellular abundance and stoichiometry of proteins Consider G-protein-coupled receptors-an expansive class of transmembrane signaling proteins that participate the potential for these techniques to advance our understanding of the role of oligomerization in G-protein-coupled
- Activation of GPR183 by 7 α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through...
GPR183 by 7 α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through Mitogen-Activated Protein Kinase and Nuclear Factor- κ B "Emerging evidence implicates the G-protein coupled receptor (GPCR) GPR183 harvested at the time of peak hypersensitivity implicate potential contributions of mitogen-activated protein
- Structure-Based Discovery of Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5
October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed
- Structural basis of GPCR coupling to distinct signal transducers: implications for biased signaling
August 2022 "Three classes of G-protein-coupled receptor (GPCR) partners - G proteins, GPCR kinases,
- Structural basis for receptor selectivity and inverse agonism in S1P5 receptors
September 2022 "The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PRs) - S1P1-5. S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads to side effects. In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 receptor in complex with a selective inverse agonist determined by serial femtosecond crystallography (SFX) at the Pohang Accelerator Laboratory X-Ray Free Electron Laser (PAL-XFEL) and analyze its structure-activity relationship data. The structure demonstrates a unique ligand-binding mode, involving an allosteric sub-pocket, which clarifies the receptor subtype selectivity and provides a template for structure-based drug design. Together with previously published S1PR structures in complex with antagonists and agonists, our structure with S1P5-inverse agonist sheds light on the activation mechanism and reveals structural determinants of the inverse agonism in the S1PR family." Read more at the source #DrGPCR #GPCR #IndustryNews
- PAR-Induced Harnessing of EZH2 to β-Catenin: Implications for Colorectal Cancer
September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing
- Interacting binding insights and conformational consequences of the differential activity of...
conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled modulate different receptors in the endocannabinoid system, some of which belong to the family of G-protein-coupled investigate the interacting determinants of CBD in two closely related endocannabinoid-activated GPCRs, the G-protein-coupled
- Structural insights into adhesion GPCR ADGRL3 activation and Gq, Gs, Gi, and G12 coupling
November 2022 "Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies A comparison of Gq, Gs, Gi, and G12 engagements with ADGRL3 reveals the key determinant of G-protein Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling
- A cryptic mode of GPCR regulation revealed
October 2022 "Over three decades of research have provided thorough insights into G protein-coupled receptor Eliminating β2AR S-nitrosylation by mutation of C265 augments β2AR protein kinase A signaling, enables β2AR nitric oxide (NO) signaling, renders mice resistant to bronchoconstriction, and protects mice from
- Successful prednisolone or calcimimetic treatment of acquired hypocalciuric hypercalcemia caused...
This emphasizes the importance of the Gi/o (pertussis toxin-sensitive G proteins, whose βγ subunits activate
- RGS7-ATF3-Tip60 Complex Promotes Hepatic Steatosis and Fibrosis by Directly Inducing TNFα
Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent
- Neuronal Gα subunits required for the control of response to polystyrene nanoparticles in the ...
polystyrene nanoparticles in the range of μg/L in C. elegans The aim of this study was to identify Gα proteins mediating function of neuronal G protein-coupled receptors (GPCRs) in controlling the response to polystyrene an animal model, and both gene expression and functional analysis were performed to identify the Gα proteins Therefore, neuronal Gα proteins of GOA-1, GSA-1, and GPA-10 functioned to transduce signals of multiple
- Integrative model of the FSH receptor reveals the structural role of the flexible hinge region
follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled
- ADGRL3 genomic variation implicated in neurogenesis and ADHD links functional effects to the...
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
- Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected to...
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
- High hedgehog signaling is transduced by a multikinase-dependent switch controlling the...
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
- GPR108 is required for gambogic acid inhibiting NF-κB signaling in cancer
Herein, we identified GPR108, a GPCR protein described in innate immune system, is a potential therapeutic
- Function and structure of bradykinin receptor 2 for drug discovery
October 2022 "Type 2 bradykinin receptor (B2R) is an essential G protein-coupled receptor (GPCR) that
- Isoforms of GPR35 have distinct extracellular N-termini that allosterically modify...
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
- HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G 1/S cycle
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 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
- In vivo metabolic effects after acute activation of skeletal muscle G s signaling
Methods: To address this question, we studied mice that express a Gs-coupled designer G protein-coupled
- Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy...
One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled
- Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer cell...
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
- Coordinated transcriptomics and peptidomics of central nervous system identify neuropeptides and ...
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
- Pharmacological targeting of cGAS/STING-YAP axis suppresses pathological angiogenesis and...
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
- Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric...
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
- Allosteric modulation of GPCRs: From structural insights to in silico drug discovery
October 2022 "G protein-coupled receptors (GPCRs) play critical roles in human physiology and are one
- Rescue of Cell Surface Expression and Signaling of Mutant Follicle-Stimulating Hormone Receptors
Mutations in G protein-coupled receptors (GPCRs) underlie numerous diseases.