As activation and recruitment of effector proteins might influence each other, thorough analysis of bias acetylcholine receptor M3 by utilizing FRET-based assays. in the presence of inhibitors of Gi and Gq proteins and analyzed arrestin3 binding to prestimulated M3 We measured substantial differences in the agonist efficacies to induce M3R-arrestin3 versus M3R-GRK2 for arrestin3 binding to M3R are distinct.

M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science. Nature Methods , 11 (8), 801-807. Heydenreich, F. M., Marti-Solano, M., Sandhu, M., Kobilka, B. ., Bouvier, M., & Babu, M. M. (2023). M., Tomašević, N., ... & Carreira, E. M. (2024). D., Muñoz, L. L., Gregory, K. J., White, P. J., Sexton, P. M., Christopoulos, A., & May, L.

Based on an ingenious combination of multicolor single-molecule microscopy approach with molecular dynamics M., Medel-Lacruz, B., Baidya, M., Makarova, M., Mistry, R., Goulding, J., Drube, J., Hoffmann, C., Owen M., Shukla, A. K., Selent, J., Hill, S. J., & Calebiro, D. (2023). M., Kawakami, K., Masureel, M., Maeda, S., Garcia, K. C., von Zastrow, M., Inoue, A., & Kobilka, B. I., & von Zastrow, M. (2001).

M. Aragay et al. 1998). Removal of G proteins by using CRISPR KO of Gαi (Gαi KO) or KO of all Gα subtypes (Gα_all KO) (M. constitutively internalize through clathrin-coated pits independently of phosphorylation and β-arrestin (M. M. Paing et al. 2022; J. L. Sapmaz et al. 2019, M. N. J. Seaman 2012).

In ascomycete fungi including yeasts, mating between cells of opposite mating type depends on the molecular The fission yeast Schizosaccharomyces pombe has two mating types, Plus (P) and Minus (M). Here, we investigated the stringency of the two GPCRs, Mam2 and Map3, for their respective pheromones , P-factor and M-factor, in fission yeast. important for discrimination of closely related M-factors.

Catch up on missed episodes and enjoy the visual experience! Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation, Migration, and Cellular with acute myocardial infarction GPCRs in Neuroscience Voltage tunes mGlu5 receptor function, impacting GLP-1 Receptor Agonist GSBR-1290 Crinetics Pharmaceuticals Appoints Robert M. Cuddihy, M.D., as Senior Vice President of Medical Affairs Septerna to Participate in the Jefferies Global

This week's highlight includes congrats to: Makaía M Papasergi-Scott, Peter Gmeiner, Brian K Kobilka, If you missed it, don't worry – you can catch the sessions on-demand with a premium membership. Are you free for a few minutes? Myers Squibb GPCR Events, Meetings, and Webinars March 23 - 24, 2024 | Ligand Recognition and Molecular May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024

of G-protein-coupled receptors "Neural network (NN)-based protein modeling methods have improved significantly Although the overall accuracy of the two non-homology-based modeling methods, AlphaFold and RoseTTAFold This work directly compares the performance of these novel deep learning-based protein modeling methods for GPCRs with the most widely used template-based software-Modeller. root-mean-square deviation (RMSD) metric.

October 2022 Mechanistic Understanding of the Palmitoylation of Go Protein in the Allosteric Regulation Hence, we performed extensive large-scale molecular dynamics (MD) simulations of the GPR97-Go complex The conformational landscapes analyzed by Markov state models revealed that the overall conformation Our study provides mechanistic insights into the regulation of aGPCRs via post-translational modifications Read more at the source #DrGPCR #GPCR #IndustryNews

causing human diseases with high mortality, such as septicemia and meningitis. The molecular mechanisms N. meningitidis employ to manipulate the immune system, translocate the mucosal However, only a small fraction of these metabolites has been identified from the human microbiota thus During this process, we also characterized two mammalian N-acyl amides derived from the bovine medium Both groups of metabolites suppress anti-inflammatory interleukin-10 signaling in human macrophage cell

October 2022 "Single-molecule counting techniques enable a precise determination of the intracellular abundance and stoichiometry of proteins and macromolecular complexes. vital physiological functions making them a popular target for drug development. and the emerging technique of quantitative single-molecule localization microscopy-with a particular Read more at the source #DrGPCR #GPCR #IndustryNews

KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined as a regulator of appetite/hunger balance mechanisms mostly up to date. In addition to its function about weight gain and appetite control mechanisms of MC3R, recent studies Despite the drastic effects of the MC3R deficiency in humans and other mammals, its cellular mechanisms In this review paper, we aimed to point out the importance of the MC3R regulations in three main concepts

They can also function independently of GPCR activation upon acquiring mutations that prevent GTPase activity and result in constitutive signaling, as occurs with the αqQ209L mutation in uveal melanoma. the addition of membrane-binding motifs enhanced PM localization and prevented YM-promoted redistribution mutants is specific to constitutively active αqQ209L. Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Mechanism of enhanced sensitivity of mutated β-adrenergic-like octopamine receptor to amitraz in honeybee Apis mellifera: An insight from MD simulations "Background: Amitraz is one of the critical However, the underlying molecular mechanism of the enhanced sensitivity or toxicity of amitraz to mutated Here, molecular dynamics simulations are employed to explore the implied mechanism of the enhanced sensitivity to amitraz in mutant honeybee Octβ2R."

skin dysbiosis and bacterial infection "Healthy skin maintains a diverse microbiome and a potent immune This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion Read more at the source #DrGPCR #GPCR #IndustryNews

coupled receptors (GPCR) to modulate cAMP levels. regulates cellular metabolism and emotional and stress responses making it integral in the maintenance processes in adipose tissue, liver, pancreas, adrenal, skeletal muscle, and gut. Mouse models have provided invaluable information on the roles for PKA subunits in brain and key metabolic Read more at the source #DrGPCR #GPCR #IndustryNews

carriers that uncouple oxygen intake by the electron transport chain from ATP production in the inner membrane of the mitochondria. UCPs are hypothesised to be triggered by superoxide and then reduce mitochondrial free radical production , potentially protecting diabetes mellitus patients who are experiencing oxidative stress. Read more at the source #DrGPCR #GPCR #IndustryNews

Microglia are one of few cell types with a self-contained endocannabinoid system and are positioned at has produced conflicting results with respect to the effects of pro-inflammatory conditions on the microglial Here we show that lipopolysaccharide and interferon gamma influence messenger RNA abundances of the microglial endocannabinoid system in a concentration-dependent manner. Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 "Study of small molecule binding to live cells provides important information on the characterization Here we developed and validated a label-free, liquid chromatography-mass spectrometry (LC-MS) based cell In one example, to study a G protein coupled receptor (GPCR), we used one antagonist as probe and multiple This versatile method allows quantitative characterization of ligand binding to cell surface expressed Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 Increased Anxiety-like Behaviors in Adgra1-/- Male But Not Female Mice are Attributable forced-swim tests, and comparable learning and memory abilities in the Morris water maze, Y maze, fear mice. Finally, we found that PI3K/AKT/GSK-3β and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly activated when compared to wt male mice.

Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of VLGR1 was previously found as membrane-membrane adhesion complexes and focal adhesions. with both the ER and mitochondria, as well as mitochondria-associated ER membranes (MAMs), a compartment Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. in the MAM architecture and in the dysregulation of the Ca2+ transient from ER to mitochondria.

A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule Read more at the source #DrGPCR #GPCR #IndustryNews

October 2022 High hedgehog signaling is transduced by a multikinase-dependent switch controlling the oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of the hedgehog (HH) morphogen of SMO in the most basal domain of the cell membrane. provide a novel mechanism for the regulation of a GPCR." Read more at the source #DrGPCR #GPCR #IndustryNews

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 Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. conceptualizing the primacy of the 3D structure over individual motifs of receptors. Read more at the source #DrGPCR #GPCR #IndustryNews

resulted in a wealth of GPCR structures that have been used in drug design and formed the basis for mechanistic cannabinoid receptor 1 (CB1R), β2 adrenergic receptor (β2 AR) and A2A adenosine receptor (A2A AR). " Read more

October 2022 Recurrent hypoglycemia increases hepatic gluconeogenesis without affecting glycogen metabolism within liver, white adipose tissue and skeletal muscle. Methods: Using a widely adopted rodent model of 3-day recurrent hypoglycemia, we first checked expression Additionally, we measured circulating FFA and glycerol to check lipolysis. Read more at the source #DrGPCR #GPCR #IndustryNews

protein-coupled receptors (GPCRs) play critical roles in human physiology and are one of the prime targets for marketed development of ligands targeting the binding site of endogenous ligands (orthosteric site), allosteric modulators Recent advances in the structure determination of GPCRs bound to different types of allosteric modulators have led to the identification of multiple allosteric sites and significantly enhanced our understanding Read more at the source #DrGPCR #GPCR #IndustryNews