September 2022 Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of To understand the basis of the ligand preferences of the receptors and to assist structure-based drug Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison

October 2022 "Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with Gq, Gs, Gi, G12 and G13. The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G12 and GPCR/G13 engagements. A comparison of Gq, Gs, Gi, G12 and G13 engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates Gq/Gs engagements from Gi/G12/G13 engagements. This is also where Gq/Gs bind the receptor through both hydrophobic and polar interaction, while Gi/G12/G13 engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Signaling pathways activated by sea bass gonadotropin-inhibitory hormone peptides in COS for the existence of a functional gonadotropin-inhibitory hormone (GnIH) system in the European sea bass Herein, we further elucidated the intracellular signaling pathways mediating in sea bass GnIH actions and the potential interactions with sea bass kisspeptin (Kiss) signaling. These data indicate that sea bass GnIHR signals can be transduced through the PKA and PKC pathways, and

“ A substitution of one amino acid by another in a protein can have effects ranging from negligible to large-scale datasets, allowing researchers to determine the functional consequences of every possible amino acid ligand-receptor interactions, mutagenesis fills crucial knowledge gaps by revealing how specific amino acid Structure-based discovery of A2A adenosine receptor ligands. Flipping the GPCR switch: Structure-based development of selective cannabinoid receptor 2 inverse agonists

characterized SK and SKR genes in the D. armandi and carried out bioinformatics predictions on the basis of the deduced amino acid sequences, which are very similar to those from Dendroctonus ponderosa. mortality of D. armandi and also led to an increase in trehalose and a decrease in glycogen and free fatty acid

as two distinct isoforms that differ only in the length of their extracellular N-termini by 31 amino acids To better understand the structural basis for this bias, we examined structural models of GPR35 and conducted isoform-specific GPR35 ligands that selectively modulate GPR35-transducer interactions and allow for mechanism-based

Therapeutics (SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based agreement with Indivior PLC (LON: INDV) for discovering and developing novel oral gamma-aminobutyric acid

GPCRs are divided into six classes based on amino acid sequence similarities, but only four of the classes

Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach

Cardiology, Endocrinology, and Taste Pathogenic variants of the GNAS gene introduce an abnormal amino acid Oncogenic signaling of the free-fatty acid receptors FFA1 and FFA4 in human breast carcinoma cells. Establishment of a CaCC-based Cell Model and Method for High-throughput Screening of M3 Receptor Drugs Oligomerization of the heteromeric γ-aminobutyric acid receptor GABAB in a eukaryotic cell-free system

Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination

GPCR Binders, Drugs, and more Discovery of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid peptide receptors Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid by directing GPCR and lipid second messenger signaling Methods & Updates in GPCR Research An image-based

Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid

GPCR Activation and Signaling Butyrate potentiates Enterococcus faecalis lipoteichoic acid-induced inflammasome A Vaccinia-based system for directed evolution of GPCRs in mammalian cells. Year ended 31 December 2022 Addex Raises $5.0 Million in Equity Financing Testing the limits of SMILES-based FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion Meeting IRN I-GPCRNet (October 25 - 27, 2023) GPCR Jobs NEW Convergent Research - Senior Scientist, Cell-Based

Molecular mechanism of fatty acid activation of FFAR1. Structure-based pharmacophore modeling 1. Automated random pharmacophore model generation. Lysophosphatidic acid, a simple phospholipid with myriad functions. 2023) GPCRs in drug discovery: challenges & solutions (June 19 - 23, 2023) Training School on “Cell-based

(GPCRs) have been identified as a new generation of attractive targets for RNA interference (RNAi)-based Results: The complementary DNA (cDNA) sequence and deduced amino acids of HLGR2 were obtained and analyzed expansion and maturation in H. cunea, suggesting HLGR2 is a promising candidate for application in RNAi-based

G-protein coupled receptors (GPCRs) depends on different molecular mechanisms triggered by conserved amino acid

In the present work, we explored the molecular basis of cholesterol-induced thermal stability of the this, we explored the possible role of the K101 residue in a cholesterol recognition/interaction amino acid

Through cell-based assays and Cryo-EM of high quality, it was possible to know that ADGRL3 can activate Interestingly, it was also reported that rearrangements of the TMs lead to a group of five hydrophobic amino acids the -4 position of αH5 was key for the selectivity of G-protein coupling, since the change of amino acids -Q., et al., Structural basis for the tethered peptide activation of adhesion GPCRs. Qu, X., et al., Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.

GPCRs in Cardiology, Endocrinology, and Taste Structure-based design of novel melanin-concentrating hormone receptor-1 ligands based on saturated nitrogen-containing heterocycles. Endogenous l- to d-amino acid residue isomerization modulates selectivity between distinct neuropeptide Structural basis for motilin and erythromycin recognition by motilin receptor. NEW Training School on “Cell-based assays to study Adhesion GPCR function".

After discussing the fundamentals and applications of mutagenesis in GPCR studies (Lu, 2024), a case This paper thoroughly investigated the role of single amino acid changes to clarify the molecular mechanisms This case study underscores the critical importance of mutagenesis in GPCR research. By understanding how different SNPs affect β2AR function, it becomes possible to tailor therapies based Molecular basis of proton-sensing by G protein-coupled receptors. bioRxiv .

interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid

cancer mutations across class A GPCRs and found a nonrandom distribution of positions with variant amino acid discovered that no single receptor drives this pattern, but rather multiple receptors contain amino acid

Structural and Molecular Insights into GPCR Function Lysophosphatidic acid, a simple phospholipid with FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion Scientist - Antibody Engineering Scientist—Immuno-Oncology Convergent Research - Senior Scientist, Cell-Based

The medium chain fatty acid receptor GPR84 as well as formyl peptide receptor 2 (FPR2), receptors expressed

September 2022 "Chemerin is the product of the RARRES2 gene which is secreted as a precursor of 143 amino acids

Establishment of a CaCC-based Cell Model and Method for High-throughput Screening of M3 Receptor Drugs Reviews, GPCRs, and more Short-chain fatty acids: possible regulators of insulin secretion. Therapeutics Announces Global Licensing Agreement with Lilly for Peripheral Pain Candidate, CFTX-1554 Cardiff-based Approach to Modern Drug Discovery Arcoscreen will present in the start-up village at Future Labs Live Basel

Although mature forms of PTHrP in the body consist of splice variants of 139, 141, and 173 amino acids Furthermore, we show that the molecular basis for biased signaling differences between PTHrP1-36 and