September 2022 "The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PRs) - S1P1-5. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 receptor demonstrates a unique ligand-binding mode, involving an allosteric sub-pocket, which clarifies the receptor

influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors within myotubes and tissues of skeletal muscle from both murines and humans, thus representing a potentially The impact of ACEA is inhibited by the selective CB1 receptor antagonist, rimonabant. The present research demonstrated that 10 nM of ACEA notably amplified mRNA gene expression of NR4A1 and NR4A3; this effect was suppressed by the addition of 100 nM rimonabant.

September 2022 "Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT2A receptor A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated

Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor

(GPCRs) like the glucagon-like peptide-1 receptor (GLP-1R). For instance, the interaction of GLP-1 with ECL3, which leads to a tight conformation of the receptor's AZIETAKU, J.T., Profiling Glucagon-Like Peptide -1 Receptor Transducer Coupling, Signalling and Biased ., The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.   Willard, F.S., et al., Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.  

Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor

October 2022 "The canonical model for G protein-coupled receptors (GPCRs) activation assumes that stimulation signaling upon ligand binding occurs solely at the cell surface and that duration of the stimulation is transient In this model, GPCR signaling is turned-off by receptor phosphorylation via GPCR kinases (GRKs) and subsequent recruitment of β-arrestins, resulting in receptor internalization into endosomes. This is the case for the parathyroid hormone (PTH) type 1 receptor (PTHR), which engages on sustained

Bursicon receptor gene HLGR2 as a potential RNA interference target for control of the fall webworm Hyphantria cunea Background: Insect G protein-coupled receptors (GPCRs) have been identified as a new generation

October 2022 "Protease activated receptors (PARs) are among the first receptors shown to transactivate other receptors: noticeably, these interactions are not limited to members of the same family, but involve receptors as diverse as receptor kinases, prostanoid receptors, purinergic receptors and ionic channels the evidence for PAR interactions with members of their own family, as well as with other types of receptors pathological relevance of these interactions, since this additional level of molecular cross-talk between receptors

all these situations, chemokines interact with seven-transmembrane chemokine-type G protein-coupled receptors (chemokine receptors, CKRs) and glycosaminoglycans (GAGs) to regulate the movement of leukocytes throughout In humans there are approximately 45 chemokines, 19 chemotactic or G-protein coupled chemokine receptors (CKRs) that signal via Gαi and 4 official atypical chemokine receptors (ACKRs) which engage in ligand To comprehensively elucidate the role of scavenging in normal physiology and the potential implications

August 2022 A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer "Adhesion G protein-coupled receptors (adhesion GPCRs), as a member of the G protein-coupled receptors (GPCRs) superfamily, have gradually entered the field of vision of

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined review paper, we aimed to point out the importance of the MC3R regulations in three main concepts: 1)

August 2022 "As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor

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

September 2022 "The complement fragment C5a is one of the most potent proinflammatory glycoproteins C5a is established to interact with a set of genomically related transmembrane receptors, like C5aR1 The C5aR1 is a classical G-protein-coupled receptor (GPCR), whereas C5aR2 is a nonclassical GPCR that tailors immune cell activity potentially through β-arrestins rather than G-proteins. The computational modeling and the 1.5-μs molecular dynamics data presented in the current study are

August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, behavior, and neurophysiology "The awareness of the potential importance of functional selectivity/biased A major pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent the past two decades, it is only recently that highly β-arrestin biased ligands for the dopamine D1 receptor

) which reveal common structural features, such as the presence of seven transmembrane domains (TMs 1- characterized by a seven transmembrane (7TM) fold structure consisting of three intracellular loops (ICLs 1- 3) and three extracellular loops (ECLs 1-3). activation: a) Route 1 - hydrogen bonding to Y2516.51 by CCL3 or CCL5; b) Route 2 - characterized by that the stability of the salt bridge depends on the position of NH2, which is most stable at position 1

Class B G protein-coupled receptors (GPCRs) are notoriously difficult to target by small molecules because Using the parathyroid hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination Here we found a key mechanical site that modulates the collective dynamics of the receptor and used this

August 2022 "The cannabinoid CB1 receptor is the most abundant G protein coupled receptor (GPCR) A variety of ligands for CB1 receptors have been developed as promising drug candidates for the treatment New high-resolution structures of CB1 receptor in different functional states have significantly improved In this review, we describe the structural determinants for modulation of CB1 receptors by different types of ligands, as well as the differences between CB1 and its homologous, the CB2 receptor.

Prokineticins (PKs) exert their biological functions through the activation of the G protein-coupled receptors (GPCRs) prokineticin receptor 1 and 2 (PKR1, 2), and mutations in the PK2 and PKR2 genes are involved We have previously shown interaction between PKR2 and anosmin 1 in vitro. (FnIII.1) suggest the cysteine-rich (CR) and the FnIII.1 domains could assist the WAP domain both in the binding to PKR2 and in the modulation of the activation of the receptor by PK2.

April 2022 "By Sophie Bradley | Apr 12, 2022 Summary Sophie Bradley, Translational Sciences Associate performed both at Sosei Heptares and Glasgow University characterizing the role of the muscarinic M1 receptor in cognitive and neurodegenerative disorders and the potential therapeutic benefit of muscarinic M1

October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed this work, molecular docking screens for allosteric modulators targeting the metabotropic glutamate receptor The mGlu5 receptor is activated by the main excitatory neurotransmitter of the nervous central system The mGlu5 receptor is a promising target for the treatment of psychiatric and neurodegenerative diseases Chemical libraries containing fragment- (1.6 million molecules) and lead-like (4.6 million molecules)

October 2022 Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Quantum Chemical Calculations "Allosteric modulators are called promising candidates in G protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation. Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors

Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor, which couples to both Gq and Gi proteins, and the MT2 receptor, which Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10-100 µM) or the nonselective MT1/MT2 agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin significantly potentiated

potential target for immunotherapy, which is reflected on the amount of ongoing clinical trials (currently bioavailability, and frequency of administration are particularly rigorous for this class, as the majority of potential ((Zimmermann, Conkright, and Rothenberg 1999). Overall, the future potential lies in using different therapeutic modalities to modulate the stromal system in different malignancies is crucial to avoid potential side effects and enhance the efficacy

August 2022 "Abstract Sigma receptor is a transmembrane non-GPCR protein expressed mainly in the endoplasmic It is classified into two types: Sigma-1 (S1R) and Sigma-2 (S2R) based on their biological functions. Therefore, S1R ligands possess a variety of potential clinical applications with a great interest in 6c resulting in 100% displacement and a Ki of 95.5 nM. Upon optimization, this series of compounds could represent potential clinically useful S1R ligands for

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker [BMB Reports 2021; 54(12): 601-607]. Read full article

September 2022 "Introduction Protease activated receptors 1 (PAR1) and 4 (PAR4) agonists are used to Flow-cytometric measurements were performed in 5, 10 and 15 min after activation."