GPCRs are present in a range of conformations, and the binding of a ligand, as well as interactions with signaling molecules like G proteins, can selectively stabilize specific conformations (Gether 2000). , and an inactive state in which their affinity for agonists diminishes in the absence of G proteins Depending on the specific functional outcome measured (e.g. activation, interaction with accessory proteins Overall, GPCRs are intriguing molecules that deviate from typical textbook proteins.

resonance (NMR) spectroscopy allows the determination of atomic-level information on intermolecular interactions In particular, we focus on the application of on-cell NMR spectroscopy to characterize ligand interactions with cell surface membrane proteins such as G-protein coupled receptors (GPCRs) and receptor tyrosine Interestingly, it is possible to avoid the barriers of production and purification of membrane proteins

August 2022 "The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3's best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3's full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans." Read more at the source #DrGPCR #GPCR #IndustryNews

Opioid receptors are G-protein-coupled receptors (GPCRs) part of cell signaling paths of direct interest 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 dynamics of opioid receptors from the perspective of the usefulness of computational studies to evaluate protonation-coupled opioid-receptor interactions.

That precursor is inactive, but proteases from the coagulation and fibrinolytic cascades, as well as Chemerin can signal via two G protein-coupled receptors, chem1 and chem2, as well as be bound to a third the specific tissue expression of the components of the chemerin system, and the role of different proteases

September 2022 "The Smoothened receptor (SMO, a 7 pass transmembrane domain, Class F GPCR family protein In the absence of HH signaling, SMO is inhibited by Patched 1 (PTC1; a 12 pass transmembrane domain protein We are able to identify the interaction of membrane cholesterols with definite sites and domains within We show that cholesterol interactions with the transmembrane domain TMD, unlike those with the cysteine-rich We have also reported the interaction of phosphatidylinositol 4-phosphate with the intracellular region

We uncovered a novel neuroprotective mechanism involving interaction between neurotrophic factor-α1 ( NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin receptor with no previously Co-immunoprecipitation and pull-down assays confirmed interaction between NFα1/CPE and 5-HTR1E and 125I Molecular dynamics studies revealed that NF-α1/CPE interacts with 5-HTR1E via 3 salt bridges, stabilized Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB

avoiding interactions with non-cognate G proteins [1]. This unproductive coupling revealed that non-cognate G protein interactions could modulate GPCR signalling This priming effect occurs through non-functional interactions between non-cognate G proteins and GPCRs interactions but also from the influence of downstream effector mechanisms. It challenges the traditional view of strict cognate G protein coupling and suggests a more dynamic interaction

This interaction significantly increases the receptor’s affinity for GTP, allowing a detailed observation of its interaction with the Gs protein in its activated state. This early interaction sets the stage for a cascade of significant conformational changes. approach is valuable for understanding the dynamics of other complex signaling pathways and molecular interactions Time-resolved cryo-EM of G-protein activation by a GPCR. Nature (2024).

September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing

β-arrestins (βarrs) play multifaceted roles in the function of G protein-coupled receptors (GPCRs). βarrs typically interact with phosphorylated C-terminal tail (C tail) and transmembrane core (TM core) of However, the effects of the C tail- and TM core-mediated interactions on the conformational activation Here, we show the conformational changes for βarr activation upon the C tail- and TM core-mediated interactions Our NMR analyses demonstrated that while the C tail-mediated interaction alone induces partial activation

One fascinating aspect of the cellular signaling network is the crosstalk between G protein-coupled receptors involvement in a myriad of physiological processes, mediate mostly signaling through heterotrimeric G proteins The interaction between these two receptor types raises intriguing questions about how their signaling Recently, Suchismita Roy et al. have explored how growth factors can modulate canonical G protein signaling The researchers focused on the phosphorylation of the G protein subunit Gαi at specific residues within

September 2022 Ginsenoside Rg5 allosterically interacts with P2RY12 and ameliorates deep venous thrombosis

G protein-coupled receptors (GPCRs) are membrane-bound proteins that sense external stimuli and relay These dimeric interactions may contribute to the phenomenon of biased agonism, where ligands produce Bouvier, M., Oligomerization of G-protein-coupled transmitter receptors.   Guo, W., et al., Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface Wootten, D., et al., Allostery and Biased Agonism at Class B G Protein-Coupled Receptors.  

Garcia-Marcos for their work on Get ready to sharpen your tools:A short guide to heterotrimeric G protein Michel Bouvier , et al. for their study on the Role of the V2R-βarrestin-Gβγ complex in promoting G protein chagas disease vector Rhodnius Prolixus (Stål ) Role of the V2R-βarrestin-Gβγ complex in promoting G protein Receptor Influence of the Water Model on the Structure and Interactions of the GPR40 Protein with the Membrane and the Solvent: Rigid versus Flexible Water Models Probing the energy landscape of the lipid interactions

Its groundbreaking ability to accurately predict protein structures is transformative for identifying The AlphaFold database encompasses over 200 million proteins, aiding structural biology, protein design Moreover, advanced AI models like AlphaFold3, which can predict complex protein-molecule interactions interactions. Accurate structure prediction of biomolecular interactions with AlphaFold 3.

A rational drug discovery campaign hinges on a deep understanding of how distinct molecules interact as X-ray crystallography and cryo-electron microscopy, have successfully elucidated ligand-receptor interactions targeted (site-directed) approaches, mutagenesis can provide a comprehensive understanding of how drugs interact with different receptor regions and link these interactions to functional variations. specific ligand interactions, such as those at the adenosine A 1  adenosine receptor (Nguyen et al.,

Transporting Protein-coupled receptors (GPCRs) to the synapse, where they are involved in neurotransmission The t-SNARE complex and VAMP2 interact to form the SNARE complex, which is essential for the fusion of In addition, VAMP2 can interact with other GPCRs, such as the beta-2 adrenergic receptor and the mu-opioid integrity of its bi-leucine sequence (which is considered a key element in its recycling), which can interact Since MOR receptor regulates pain perception and reward, the dysfunction in the MOR-SNARE complex interaction

It is primarily coupled to the Gs protein, which leads to the production of cyclic AMP (cAMP). In contrast, ligands like oxyntomodulin that preferentially activate ERK1/2 signaling interact more significantly For instance, the interaction of GLP-1 with ECL3, which leads to a tight conformation of the receptor's transmembrane domain (TM), contrasts with the looser interaction seen with biased agonists like exendin-P5 These agonists exhibit less interaction with ECL3, resulting in an open conformation of the TM6-ECL3-

August 2022 A new Kunitz-type snake toxin family associated with an original mode of interaction with and non-active V2R Kunitz peptides highlighted five positions, among which four are involved in V2R interaction We finally determined that eight positions, part of these two loops, interact with the V2R.

, for their work on Conformation- and activation-based BRET sensors differentially report on GPCR-G protein GPCR Activation and Signaling GPCR-dependent and -independent arrestin signaling Direct GPCR-EGFR interaction required for Shh-mediated axon guidance GPCRs in Oncology and Immunology Regulator of G protein signaling coupling Reviews, GPCRs, and more Proteome-wide analysis reveals G protein-coupled receptor-like proteins in rice (Oryza sativa) G Protein-Coupled Receptors: A Century of Research and Discovery Challenges and

genetic disease Ilana Kotliar , Thomas Sakmar , et al. for their study on Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins Nicholas Kapolka , Geoffrey Taghon , and Daniel Isom and Signaling ONE-GO: Direct detection of context-dependent GPCR activity Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins Molecular mechanism of bitter taste receptor agonist-mediated new life into schizophrenia pipeline GPCR Dynamics Reveal Mechanisms for Drug Discovery DMS: Linking Protein

GPCR Activation and Signaling The G protein alpha chaperone and guanine-nucleotide exchange factor RIC distinct functions Phosphorylation motif dictates GPCR C-terminal domain conformation and arrestin interaction Signaling Protocol for identifying physiologically relevant binding proteins of G-protein-coupled receptors targeted protein degradation techniques Ligand selectivity hotspots in serotonin GPCRs Study of G protein-coupled ligands to drug-like small molecules Structural and Molecular Insights into GPCR Function Hydrophobic interaction

CXV: The Class F of G Protein-Coupled Receptors Yusman Manchanda , Dr. Alejandra Tomas , et al. for their research on Engineered mini-G proteins block the internalization of receptor drug discovery The application of targeted protein degradation technologies to G protein-coupled receptors Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics CXV: The Class F of G Protein-Coupled Receptors Structural and Molecular Insights into GPCR Function

September 2022 CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma signaling pathway "Background CC chemokine receptor 9 (CCR9), an organ-specific chemokine receptor, interacts Western blot and RT–qPCR assays were carried out to measure the downstream factors of the interaction

meningitidis and identified 30 N-acyl amides with representative members serving as agonists of the G-protein

interactions, particularly the differences between Gs and Gi/o coupling. complexes revealed two important aspects: the specific residues involved in ligand selectivity and the interactions involved in the coupling of G proteins. interactions are crucial for the coupling of G-proteins to serotonin receptors. The TM5 extension of receptors Gs-coupled provides unique interactions that are not seen in complexes

Activation and Signaling Palmitoylation of the Glucagon-like Peptide-1 Receptor Modulates Cholesterol Interactions at the Receptor-Lipid Microenvironment Basal interaction of the orphan receptor GPR101 with arrestins leads to constitutive internalization Identification of G Protein-Coupled Receptors (GPCRs) Associated mediate somatostatin responsiveness via SSTR3 Inhibition of a novel Dickkopf-1-LDL receptor-related proteins NLRP3 degradation Methods & Updates in GPCR Research Direct Binding Methods to Measure Receptor-Ligand Interactions