systematically investigated the relationship between the concentration of two distinct pro-inflammatory stimuli, lipopolysaccharide Here we show that lipopolysaccharide and interferon gamma influence messenger RNA abundances of the microglial

October 2022 ADGRL3 genomic variation implicated in neurogenesis and ADHD links functional effects to found that nsSNPs rs35106420, rs61747658, and rs734644, previously reported to be associated and in linkage harbored in the ADGLR3-hormone receptor domain (HRM, a common extracellular domain of the secretin-like GIP has been linked to the pathogenesis of diabetes mellitus, and our analyses suggest a potential link showed that functional mutations in the ADGLR3 gene disrupt the standard and wild ADGRL3 structure, most likely

October 2022 Increased Anxiety-like Behaviors in Adgra1-/- Male But Not Female Mice are Attributable potential role of ADGRA1 in the neurobehaviors of mice by comparing Adgra1-/- and their wild-type (wt) littermates male but not female mice exhibited elevated anxiety levels in the open field, elevated plus maze, and light-dark

While GPCRs can exist as monomers, some types, like class C GPCRs, are obligate dimers, either as homodimers For example, dimerization has been shown to affect signaling pathways in class A dopamine receptors like to its natural ligand, GLP-1, while selectively affecting receptor signaling. binding, and downstream signaling. Harikumar, K.G., et al., Impact of secretin receptor homo-dimerization on natural ligand binding.  

Depending on which ligand activates a receptor, it can engage different intracellular transducers. Ligands eliciting biased signalling may constitute better drugs with higher efficacy and fewer adverse However, ligand bias is very complex, making reproducibility and description challenging. Here, we provide guidelines and terminology for any scientists to design and report ligand bias experiments receptor research and drug discovery communities continue to advance our understanding and exploitation of ligand

Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin

A variety of ligands for CB1 receptors have been developed as promising drug candidates for the treatment receptor in different functional states have significantly improved our molecular understanding of CB1 ligand These advances have paved the way for development of novel ligands for different therapeutic applications review, we describe the structural determinants for modulation of CB1 receptors by different types of ligands LINKED ARTICLES: This article is part of a themed issue on Structure Guided Pharmacology of Membrane

August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid

Using purified Fzd proteins reconstituted in lipid nanodiscs, we investigated the factors that promote We found that the affinity of Fzd for Dvl was not affected by Wnt ligands, in contrast to other members of the GPCR superfamily for which the binding of extracellular ligands affects the affinity for downstream Instead, Fzd-Dvl binding was enhanced by increased concentration of the lipid PI(4,5)P2, which is generated by Dvl-associated lipid kinases in response to Wnt and which is required for LRP5/6 phosphorylation.

Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting

In summary, our study shows that inhibiting homodimerization has a setmelanotide-like effect on Gq/11

September 2022 High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways correlation with the mRNA subtype of TNBC ( P  = 0.001), total metastatic events ( P  = 0.019) and liver Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways

September 2022 "Class A (rhodopsin-like) G protein-coupled receptors (GPCRs) are constitutive phospholipid scramblases as evinced after their reconstitution into liposomes. We considered whether cholesterol, a prominent component of the plasma membrane, limits the ability of GPCRs to scramble lipids. This mechanism may explain the inability of GPCRs to scramble lipids at the plasma membrane."

September 2022 A2B Adenosine Receptor Enhances Chemoresistance of Glioblastoma Stem-Like Cells under and the presence of a cell subpopulation that persists under hypoxic niches, called glioblastoma stem-like

September 2022 "The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an

Endogenous ligands, named endocannabinoids, are produced “on demand” to finely regulate the synthesis It is well known that immune challenges, such as exposure to lipopolysaccharide, the main component of

Corporation (“ Sosei Heptares ”; TSE: 4565) today announces that in connection with the Collaboration and License Agreement (“License Agreement”) with Neurocrine Biosciences , Inc. (“ Neurocrine Biosciences ”) announced As such, the License Agreement became effective on 22 December 2021. With completion of the applicable waiting period under the HSR Act, under the terms of the License Agreement

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."

migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding These structures reveal an agonist binding site for the oxysterol and a potential ligand entrance site exposed to the lipid bilayer. Together, these findings provide new insight into how EBI2 is activated by an oxysterol ligand and will facilitate the development of therapeutic approaches that target EBI2-linked diseases."

cells in a microplate reader assay format upon stimulation with H3R ligands. light-sensitive azobenzene moiety for photo-switching. H3R biosensor in membrane preparations and found that observed potency values better correlated with binding affinity values that were measured in radioligand competition binding assays on membranes. conformational biosensor in membranes might be a ready-to-use, high-throughput alternative for radioligand binding

determined structures of class C G protein-coupled receptors (GPCRs) revealed the location of allosteric binding 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

determined structures of class C G protein-coupled receptors (GPCRs) revealed the location of allosteric binding 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

August 2022 "The X-linked form of Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism We also show that the N-terminal region of anosmin 1, capable of binding to the PK2-binding domain of FnIII.1) suggest the cysteine-rich (CR) and the FnIII.1 domains could assist the WAP domain both in the binding

Hannes Schihada and his lab team developed fluorescent analogues for real-time binding studies of orphan Find speaker details on the Live Talks page and mark your calendar HERE. exchange factor RIC-8 regulates cilia morphogenesis in Caenorhabditis elegans sensory neurons CaSR links Binders, Drugs, and more Cloning and deorphanization of three inotocin (insect oxytocin/vasopressin-like Molecules Accurately predicting GPCR P2Y1 membrane protein ligand binding with Free Energy Perturbation

that matches its binding pocket. Small protein GPCRs feature a two-component binding mechanism in which one part of the ligand engages As seen below in Figure 1, natural ligands do not make use of all the potential binding contacts with Left: Natural ligands of small protein GPCRs use a two-component binding mechanism, with extracellular Orion’s approach to engineering ligand analogs involves leaving the ‘address’ binding interface on the

At the cellular level, the plasmatic membrane is a thin layer of lipids that surrounds the entire cell The cellular membrane's composition, organization, and physical properties might impact ligand binding Lipid molecules, such as phosphoinositides, can bind to specific domains of β-arrestins, promoting their bilayer likely contributes to stabilizing β-arrestin in a membrane-bound, active-like conformation. They shed light on the essential role of β-arrestin binding to the lipid bilayer for efficient interaction

Q. et al. 2021), that allow interaction with trimeric G proteins, which regulate second messengers like This includes proteins like AP-2 and clathrin, vital for internalization, as well as MAPK cascade kinases Thus, exploring large-scale protein-protein interaction datasets could shed light on connections between Fine-tuned systems of protein expression regulate various processes, and their imbalance is linked to Changes in the availability of regulatory proteins like GRKs can impact GPCR phosphorylation and subsequent

many aspects including the assembly of the extracellular and transmembrane domains, the shape of the ligand-binding pockets, and the conformation of the transducer-binding interfaces.