Receptor Mechanisms and Signaling

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 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.

The paper identifies a stimulant derivative binding in a cryptic vestibular pocket of the 5-HT3A receptor using computational and experimental methods.

The paper introduces the Kd/EC50 ratio as a gain parameter to quantify signal amplification for full agonists, clarifying the relationship between receptor occupancy and response.

The paper compares expression protocols for Gα subunits, showing that a new purification method enhances enzymatic activity and reveals domain interactions affecting stability.

This study identifies HCA3R as a new GPCR in human neutrophils and shows it activates NADPH oxidase with specific pre-treatment requirements.

This study shows that an allosteric modulator of FFA2R converts LTB4 into a potent NADPH oxidase activator via BLT1R-FFA2R receptor transactivation.

This study evaluates how different dopamine D1 receptor agonists activate Gαs and Gαolf, revealing region-specific pharmacological profiles with implications for targeted drug development.

This paper uses computational methods to model how nitazene derivatives bind to the mu-opioid receptor, identifying key binding modes and interactions.

This study identifies GLP-1 analogues with prolonged signaling by modifying specific amino acids, showing how receptor trafficking and peptide structure affect signaling duration.

This study identifies an arrestin-independent phosphorylation mechanism that terminates CCR9 signaling, revealing a novel regulatory pathway for GPCR function.

This study shows that agonist efficacy at the {beta}2AR is determined by differences in receptor affinity for Gs protein, not ligand binding kinetics.

This study applies high-resolution deep mutational scanning to the melanocortin-4 receptor to identify functionally significant variants and guide drug development.

This paper introduces an optical biosensor that directly detects endogenous Gαi activity in cells, showing improved sensitivity and reduced interference compared to existing methods.

This paper investigates how catechol and non-catechol dopamine D1 receptor agonists induce different signaling and endocytosis patterns, showing that functional selectivity impacts receptor internalization.

This study identifies structural features determining G protein coupling specificity at a class A GPCR using a Gi-biased agonist.

This study shows that oxysterol accumulation in aged cells disrupts CXCR4 signaling by altering G-protein coupling specificity.

This study identifies how N-glycosylation and phosphorylation in specific motifs of GPR52 differentially regulate its signaling bias and cellular function.

The paper investigates how YM-254890 specifically inhibits Gq/11 by stabilizing the G-Gβγ complex through allosteric effects, revealing its mechanism as an 'allosteric glue'.

This study uses atomic-level simulations to show how ligand binding modulates conformational dynamics of the M2 muscarinic receptor, revealing key aromatic residue interactions involved in activation.

The paper investigates how GPCR domains influence β-arrestin functions and conformational changes, revealing domain-specific effects on signaling outcomes.

The paper identifies lineage-specific expansions of Class-A GPCRs in Lophotrochozoa, linking them to habitat adaptations and chemosensory functions.

This study uses PPI-GaMD simulations to reveal dynamic mechanisms of peptide agonist dissociation and deactivation in ADGRG1 and ADGRG2.

This study evaluates the impact of an N-terminal Halo-tag on GIPR function in mice, finding reduced cAMP responses and impaired glucose tolerance in tagged mice.

The paper resolves the structure of an intermediate GPCR-G protein complex and shows it initiates nucleotide exchange without progressing to the fully activated state, providing insights into GPCR signaling complexity.

This study uses molecular dynamics simulations to analyze how serotonin, psilocin, and Gqalpha affect 5HT2A receptor conformation and binding affinity.

This study determines the structure of Drosophila ROS1's extracellular region bound to BOSS, revealing a hydrophobic interaction and beta-strand augmentation mechanism.

The paper uses a machine learning model to predict signaling efficacy through the μ opioid receptor by analyzing intracellular pocket conformations.

This study reports cryoEM structures of mGlu5 receptor with different PAMs, showing how PAM binding modulates receptor conformation and function.