Receptor Mechanisms and Signaling

This study shows that the PI3K inhibitor PI828 blocks Ca2+ responses to aminergic agonists through an unknown mechanism unrelated to PI3K inhibition, while wortmannin has minimal effect.

The paper uses biosensors to study CaSR-mediated signaling pathways in HEK-293 cells, showing activation of Gq and Gi proteins and their effects on intracellular calcium and cAMP levels.

This study shows that lipids like PIP2 and GM3 modulate the conformation of ICL3 in beta-2AR, affecting G protein coupling through membrane tilting and allosteric effects.

This study investigates the structural stability and orientation of the neurotensin receptor 1 H8-Ctail using NMR in detergent and lipid environments, revealing its sensitivity to membrane conditions.

This study presents cryo-EM structures of MCH-activated MCHR1 and MCHR2 with G-proteins, revealing ligand recognition mechanisms and activation pathways.

This study investigates how vortioxetine interacts with human and rodent 5-HT3 receptors, revealing structural differences and mechanisms of action.

The paper visualizes endogenous G proteins on endosomes and other organelles using gene editing and microscopy, showing their distribution and trafficking.

The paper analyzes GPCR signaling dysregulation in cancer transcriptomics data to identify therapeutic targets and survival-associated signaling axes.

This study uses single-molecule techniques to analyze the diffusion and oligomerization of M1R in live cells, showing ligands and membrane disruptors modulate these states.

This study uses molecular dynamics simulations to show that cholesterol modulates conformational changes in mGluR1 dimers, with 10% cholesterol causing the most significant effects.

The paper investigates the agonist activity of tetracyclic antidepressants at 5-HT1eR and 5-HT1FR, revealing unique binding poses and receptor-specific mechanisms.

This study identifies how RTK phosphorylations induce G-protein activation through structural changes and faster GDP release.

The paper shows that the cellular environment significantly affects GPCR signaling, leading to physiological bias in neutrophils that impacts drug efficacy.

This study uses in silico methods to investigate the role of calcium in the inactivation of the human olfactory receptor OR51E2, identifying a novel mechanism involving divalent ion coordination.

This study uses molecular dynamics to show that different CB1 receptor agonists induce distinct conformations leading to biased signalling through differential coupling to G proteins and beta-arrestins.

This study reveals the constitutive activity and dimerization mechanism of GPR156, explaining its role in auditory function through cryo-EM structures and functional analysis.

This paper quantifies GPCR intrinsic activation at the plasma membrane, revealing spatial multimodality with most receptors showing negligible spontaneous activation.

The paper develops a biosensor platform to measure GPCR activity in various contexts, revealing insights into coupling selectivity, pharmacogenomics, and signaling bias.

This study pharmacologically characterizes seven human H3R isoforms, finding differences in agonist and inverse agonist binding affinities, with implications for drug discovery.

This paper introduces a high-throughput BRET-based thermal shift assay to measure protein stability and ligand interactions with Gi1 protein without purification.

This study determines the structure of the CELSR1 extracellular region and shows how specific domains form a compact module to regulate cellular adhesion.

This study investigates rare disease variants in Gs, a G protein, using multidimensional approaches to reveal how mutations affect receptor-Gs coupling and signaling defects.

This study identifies stalk-derived peptides that activate PC1 signaling by binding to specific regions, revealing structural dynamics and potential therapeutic applications for ADPKD.

This study shows that Larixol does not inhibit Gi or Gq containing G proteins in human neutrophils, contradicting previous claims about its inhibitory effects on FPR1 and related receptors.

The paper shows that co-expression of G protein-coupled receptors can lead to emergent cellular behavior through a switch in downstream signaling, specifically demonstrating a reversal of dopamine D2 receptor activity.

The paper introduces a fluorescent ligand for visualizing D1 and D5 dopamine receptors, showing high affinity and selectivity with applications in fluorescence microscopy.

This study uses deep learning and simulations to reveal dynamic allostery mechanisms in GPCRs, showing modulators restrict conformational space and enhance selectivity.

The paper develops structural models of beta-1 and beta-2 adrenergic receptors with beta-blockers using RosettaLigand and MD simulations, identifying structural features and stability but not clearly distinguishing stereospecific drug preferences.

This paper describes the synthesis and characterization of fluorescent ligands for imaging and ligand screening of dopamine D2-like receptors, showing high affinity and selectivity.

The paper presents the cryo-EM structure of the human histamine H2 receptor complexed with Gs protein in lipid nanodiscs, revealing insights into ligand binding and G protein coupling mechanisms.