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 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 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 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 (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 CCR2 is an example of a dual-function receptor that directly regulates both cell migration and scavenging

October 2022 "The canonical model for G protein-coupled receptors (GPCRs) activation assumes that stimulation 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. Internalized receptors can then recycle back to the cell surface or be trafficked to lysosomes for degradation This is the case for the parathyroid hormone (PTH) type 1 receptor (PTHR), which engages on sustained

C5a is established to interact with a set of genomically related transmembrane receptors, like C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2) with comparable affinity. The C5aR1 is a classical G-protein-coupled receptor (GPCR), whereas C5aR2 is a nonclassical GPCR that

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

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

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 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed The mGlu5 receptor is activated by the main excitatory neurotransmitter of the nervous central system these, four fragment- and seven lead-like compounds were confirmed to bind to the allosteric site with affinities The four compounds with the highest affinities were demonstrated to be negative allosteric modulators fragment- and lead-like chemical libraries have complementary advantages and illustrate how access to high-resolution

Chemokine receptors (CKRs) belong to a subfamily of G-protein-coupled receptors (GPCRs) and play a crucial complexes and revealing the diverse and multifaceted nature of the chemokine receptor system. Currently, there are more than 40 available structures of chemokines and their receptors in the Protein Lackman et al. 2023), which provide extra negative charges to the N-terminus thereby increasing binding affinity US28 evolved high constitutive activity to evade host immunity, whereas ACKR3 functions as a homeostatic

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 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

Glycosylation and sulfation – N-terminal PTMs on chemokine receptors The interaction of chemokine receptors of the negatively charged aminoacids and post-translational modifications (PTMs), contribute to the high affinity binding to the positively charged groove on the chemokine. PTM has been shown to be heterogeneous [Li X et al. 2018; Scurci I et al. 2021) and to improve the affinity It has been also reported that PSGL-1 glycosulfo peptide analogue GSnP-6 displays nanomolar affinity

Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor

Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor

These studies also show that disrupting the dimerization of GLP-1R results in decreased high-affinity from the receptor’s core, which is crucial for G protein recruitment. both binding affinity and signaling potency. ), facilitating the partial disengagement of the peptide while maintaining high-potency signaling. induces G-protein-coupled receptor heteromer formation.  

The chemokine receptor system is implicated in a wide range of inflammatory, autoimmune and infectious The involvement of chemokines and their receptors in several aspects of cancer biology, represents a This redundancy can be seen as problematic in drug discovery as blocking a single receptor might not Therefore, an alternative approach is to make use of chemokine receptors redundancy and the fact that Furthermore, both chemokines and receptors can homo- and hetero-oligomerize, impacting receptor/ligand-binding

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

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

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

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,

G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor , GHSR1a The growth hormone secretagogue receptor 1a (GHSR1a) is intriguing because of its potential Initial studies of the receptor focused on the potential therapeutic ability for growth hormone (GH) At some sites, such as at somatotrophs, GHSR1a has high constitutive activity. In all cases, the receptor interaction changes downstream signalling and the responses to receptor agonists

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid The primary analgesic target of opioids is the μ-opioid receptor (MOR). found that MOR alone could not stimulate PLC, but rather required a coincident signal from a Gq coupled receptor