Receptor Mechanisms and Signaling

This study uses molecular dynamics simulations to investigate the conformational changes in β-arrestin 1 during activation by the vasopressin receptor-2.

This study shows that paroxetine enhances serotonin receptor responses in breast epithelial cells by modulating G protein subtype-specific signaling pathways, leading to reduced cell proliferation.

This study uses AlphaFold and simulations to show human SUCNR1 spontaneously adopts active conformations and exhibits constitutive signaling, while murine SUCNR1 requires agonist for activation.

This study reveals that membrane phosphoinositides allosterically regulate β-arrestin dynamics, enabling engagement with minimally phosphorylated GPCRs.

The paper identifies SNPs in GPCRs that alter β-arrestin signaling bias and shows their potential impact on phenotypic variation.

This paper shows that the actin cytoskeleton regulates NADPH oxidase activation and G protein recruitment in neutrophils via Gq-coupled receptors.

The paper introduces GPCR-MAPS, a method to generate high-resolution functional and allosteric maps of GPCRs, revealing modular architecture and novel allosteric pockets.

This study shows that PI(4,5)P2 modulates the orientation and receptor interaction of β-arrestin 1 through its interaction with the C-edge loop.

The paper identifies structural elements in Gαs that prevent interactions with RGS proteins, showing three residues in the GTPase domain are necessary and sufficient for this resistance.

This study identifies a convergent molecular mechanism and species-specific pharmacology in complement anaphylatoxin receptors through structural and functional analyses of ligand-receptor interactions.

The paper identifies two novel GPR17 antagonists through high-throughput screening that selectively inhibit GPR17 signaling and enhance GLP-1 secretion, offering potential for diabetes and obesity treatment.

This study compares the conformational equilibria of the human A2A adenosine receptor in lipid vesicles and aqueous solutions using 19F-NMR, revealing environment-dependent differences in agonist-bound states.

This study shows arrestin2 binds to the β1-adrenergic receptor independently of receptor conformation or ligand type, driven by a conformational change in arrestin induced by a phosphopeptide.

GZESTY is a cell-based assay for Gi/o/z-coupled GPCRs that detects ligand activation and identifies endogenous ligands for orphan GPCRs.

This study uses NMR to show GRK1 and GRK2 produce distinct phosphorylation patterns on C-terminal peptides of GPCRs, revealing time-dependent phosphorylation barcodes that may influence arrestin interactions during desensitization.

This study identifies and characterizes synthetic ligands for HCAR1 using ebBRET, revealing its activation of Gi/o and Gs pathways without β-arrestin recruitment.

This study uses APEX2 proteomics to map the spatiotemporal interactome of the luteinizing hormone receptor (LHR) and identifies novel interactors like RAP2B that modulate receptor signaling and trafficking.

This study shows that LHR and Gαs trafficking from endosomes sustain cAMP signaling to control steroidogenesis in Leydig cells.

This study maps how phosphorylation patterns shape β-arrestin structure and function using simulations and machine learning, revealing isoform-specific allosteric responses and effector engagement.

This study presents structural insights into PAR1 and PAR2 activation by endogenous ligands, revealing a novel mechanism and potential targets for therapeutic development.

This study identifies a pre-active intermediate in GPCR activation and shows how dimer interactions influence signaling efficacy and functional diversity.

The paper solves cryo-EM structures of the V2R bound to Tolvaptan and Mambaquaretin toxin, revealing distinct antagonist binding modes and inactive conformations.

This study uses metadynamics and Markov state models to explore the conformational dynamics of GHSR-1a, revealing ligand-dependent metastable states and intermediate structures.

The paper reports cryo-EM structures of the ETB receptor bound to the lasso peptide RES-701-3, revealing its inverse agonist mechanism through hydrophobic interactions and conformational stabilization.

This study shows that the mu-opioid receptor increases endosomal G protein activity without requiring receptor internalization or endosomal activation.

Resource of 212 literature-curated chimeric class A GPCRs linked to 1,755 natural class A mammalian GPCRs, annotated at sequence, structure and biophysics level, with guidelines for designing new chimeras.

This study determines cryo-EM structures of GPR3 in active and inactive states, revealing dimerization mechanisms and identifying a negative allosteric modulator targeting the dimerization interface.

This paper assesses GPCR-ligand complex predictions in the era of AlphaFold, showing AI models can match or exceed low-resolution experimental structures but still need high-resolution data and hybrid methods.

This paper introduces mwSuMD, a molecular dynamics algorithm, to simulate complex structural transitions in GPCRs without energy bias, demonstrating its application in studying receptor activation and GDP release.

Antimuscarinic drugs act as β-arrestin-biased agonists via casein kinase 2 activation to promote ERK1/2 phosphorylation and neurite outgrowth.