Opioid receptors are G-protein-coupled receptors (GPCRs) part of cell signaling paths of direct interest The potentially low pH at tissue targeted by opioid drugs in pain management could impact drug binding to the opioid receptor, because opioid drugs typically have a protonated amino group that contributes to receptor binding, and the functioning of GPCRs may involve protonation change. In this review, we discuss the relationship between structure, function, and dynamics of opioid receptors

The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors 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 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.

influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized The part played by CB1 receptor activation or inhibition with respect to these functions and relevant This can be deduced from the qRT-PCR assays; triggering CB1 receptors amplifies both NR4A1 and NR4A3 The impact of ACEA is inhibited by the selective CB1 receptor antagonist, 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 increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated

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 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 them from in vivo sites, while maintaining the responsiveness of canonical G protein-coupled CKRs that bind binding.

October 2022 "The canonical model for G protein-coupled receptors (GPCRs) activation assumes that stimulation of heterotrimeric G protein signaling upon ligand binding occurs solely at the cell surface and that 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

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined

August 2022 "As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous 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

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

to the receptor N-terminus (CRS1), and the N-terminus assumes diverse binding modes in the 7TM cavity binding pocket, known as CRS3 which is characterized by three different binding modes: CC chemokines with deep binding, CC/CXC chemokines with shallow binding near TM5, and CX3C chemokines with shallow binding near the ECL2 hairpin. and TM6 following chemokine binding to the upper part of CRS2.

performed both at Sosei Heptares and Glasgow University characterizing the role of the muscarinic M1 receptor

October 2022 Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation. binding location that raises many questions about the ligand interactions and stability, the binding 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

October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed the location of allosteric binding sites and opened new opportunities for the discovery of novel modulators The mGlu5 receptor is activated by the main excitatory neurotransmitter of the nervous central system 1.6 million molecules) and lead-like (4.6 million molecules) compounds were docked to an allosteric binding Of these, four fragment- and seven lead-like compounds were confirmed to bind to the allosteric site

At a molecular level, different ligands bind to the same receptor and vice-versa (Marcuzzi et al. 2018 An example is CCL5 which binds to CCR1, CCR3 and CCR5, and induces different patterns of receptor recycling Furthermore, both chemokines and receptors can homo- and hetero-oligomerize, impacting receptor/ligand-binding and signaling patterns, by modulating ligand binding, as well as G-protein coupling or interaction with An additional milestone is represented by the large binding pocket of chemokine receptors which are regulated

September 2022 "Introduction Protease activated receptors 1 (PAR1) and 4 (PAR4) agonists are used to

November 2022 "Despite the growing number of G protein-coupled receptor (GPCR) structures, only 39 structures that for each of the 21 structures with bound ligands there exist many other GPCRs that have a strong binding However, ligands binding at the same location generally show little or no similarity, and the amino acid specifically targeting these sites across GPCRs for allosteric modulation and help to identify the most likely binding

Most acquired genes are transmembrane proteins and cytokines, such as viral G protein-coupled receptors (vGPCRs), chemokines, and chemokine-binding proteins. These include receptors from human cytomegalovirus, which encodes four vGPCRs: US27, US28, UL33, and We discuss ligand binding, signaling, and structures of the vGPCRs in light of robust differences from endogenous receptors.

August 2022 "Background: Activation of signaling effectors by G-protein coupled receptors (GPCRs) depends

Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst accessible summary of the literature on Alzheimer's disease and the therapeutic potential of A1 and A2A receptors Although there are no available medicines targeting these receptors approved for treating dementia, we

Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst accessible summary of the literature on Alzheimer's disease and the therapeutic potential of A1 and A2A receptors Although there are no available medicines targeting these receptors approved for treating dementia, we

October 2022 "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. 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

binding, where the negatively charged residues, as a consequence of the negatively charged aminoacids and post-translational modifications (PTMs), contribute to the high affinity binding to the positively I et al. 2016) where O-glycosylation contributes to the differential binding to CC or CX3C chemokine tyrosine sulfation sites in their N-termini that mediate ligand binding and signaling (Bannert N et Both PTMs were shown to contribute to the binding of CCL5 and CCL8 and to a minor extend CCL3.

Thus, we investigated the regulatory functions of its β-adrenergic-like octopamine receptor (PxOctβ3) open reading frame (ORF) of PxOctβ3 was phylogenetically analyzed, and the levels of expression of the receptor A series of octopamine receptor agonists and antagonists were tested against PxOctβ3. We showed that the receptor is a member of the Octβ3 protein family, and an analysis using quantitative Furthermore, the agonists naphazoline, clonidine, 2-phenethylamine, and amitraz activated the PxOctβ3 receptor

September 2022 "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. 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

Biased agonism is a phenomenon where different ligands acting on the same receptor trigger distinct signaling is gaining significant attention in drug discovery, especially in the context of G protein-coupled receptors (GPCRs) like the glucagon-like peptide-1 receptor (GLP-1R). Additionally, GLP-1R couple to G protein-coupled receptor kinases (GRKs) and recruit β-arrestins, adding For instance, the interaction of GLP-1 with ECL3, which leads to a tight conformation of the receptor's

October 2022 "Cannabinoid Receptor 2 (CB2) is a G protein-coupled receptor (GPCR) with considerable,