Receptor Mechanisms and Signaling

This study identifies AngII analogs with modified C-terminal peptides that selectively engage Gq or β-arrestin pathways, showing differential effects on cardiac function and blood pressure in rats.

XenoSignal assesses ligand-receptor interactions across species using AlphaFold3 predictions to improve understanding of tumor-microenvironment crosstalk in xenograft models.

The paper investigates the G protein coupling profile of dopamine D3 receptor, finding it selectively activates Go and Gz subtypes but not Gi proteins, with structural determinants identified.

This paper introduces GTACs, bispecific antibodies that selectively downregulate GPCRs via endocytosis and lysosomal degradation, showing high potency and selectivity for therapeutic targets.

The paper identifies ZDHHC8-dependent Gαq palmitoylation as a critical regulator of GPCR signaling through a genome-wide CRISPR screen in Drosophila.

This paper reveals how insulin mimetics stabilize the insulin receptor in a novel apo-state that prevents activation by blocking signal transduction.

The paper presents the cryoEM structure of unliganded human GPR75 and functional data showing its active-like state and signaling properties.

This study develops a single-molecule technique to investigate cytoplasmic tail dynamics of membrane receptors in living cells, revealing ligand-induced activation mechanisms of β2AR.

This study shows that the C-terminal tail of LPHN2 modulates G protein and arrestin-3 signaling bias through alternative splicing and GRK interactions.

The paper tests eCF506, a c-Src inhibitor, showing it reduces opioid tolerance by decreasing β-arrestin2 recruitment without affecting cAMP inhibition.

This study uses smFRET to show that opioid ligands modulate Gi protein conformational dynamics, with higher-efficacy agonists promoting open, low-nucleotide-affinity states.

The paper identifies frustrated residues in GPCR:G protein interfaces and engineered degrader complexes, showing higher frustration in engineered interfaces.

This study uses constant-pH simulations to show that β2AR inactivation is linked to protonation events and sodium ion interactions, challenging existing models of GPCR function.

The paper discovers a GPR183 inverse agonist using AI-driven virtual screening and a conformational biosensor, showing inhibition of Gi activation and β-arrestin2 recruitment.

The paper shows that US28's Gq/11 signaling from the plasma membrane, not endosomes, primarily drives gene expression related to glioblastoma proliferation and inflammation.

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

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 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 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.

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