Receptor Mechanisms and Signaling

The paper shows that osmotic swelling enhances β2-adrenergic receptor activity and downstream cAMP responses in cardiomyocytes and other cell types.

This paper presents two inactive CCR6 structures bound to allosteric antagonists, revealing structural insights into CCR6 inhibition and its implications for drug discovery.

This study uses molecular dynamics simulations to compare conformational dynamics of inactive and active states of CB1 receptor, identifying key structural differences and electrostatic interactions that influence its function.

This study shows that osteocalcin binds to a distinct allosteric site in GPRC6A's VFT domain, acting as a positive modulator and enhancing its signaling.

The paper investigates the role of GRK subfamilies in phosphorylation of the MOR C-tail and their impact on β-arrestin2 recruitment, showing GRK2/3 and GRK5/6 have distinct contributions.

The paper identifies 122 GPCRs interacting with RAMPs using a DuET library and SBA assay, expanding the GPCR-RAMP interactome to inform therapeutic design.

The paper analyzes bitopic ligands for dopamine D2 and D3 receptors, showing that linker structure and stereochemistry significantly influence transducer bias profiles.

This study investigates how ETB couples to different G proteins, finding that it interacts with Gi and Gq but not Gs, with specific regions influencing these interactions.

This study investigates the conformational dynamics of ACKR3 activation using HDX-MS and molecular dynamics simulations, revealing key structural changes and ligand binding mechanisms.

The paper determines the cryo-EM structure of ligand-free human CCR8-Gi complex and identifies key residues for agonist recognition.

This paper investigates how C-terminal domains of GPCRs interact with membranes to regulate receptor function, showing that these interactions influence transducer coupling and are modulated by phosphorylation and membrane composition.

This study develops GFP-inspired dyes to monitor ligand-induced conformational changes in GPCRs, showing fluorescence responses to agonists and allosteric modulators.

This paper identifies a negative allosteric modulator of the μ-opioid receptor that blocks agonist activity and enhances naloxone efficacy, offering potential for safer opioid overdose reversal.

This paper shows that GRK2/3's interaction with Gβγ is essential for β-arrestin2 recruitment to GPCRs, linking G protein activation to biased agonism potential.

This study investigates the activation mechanism of GPR68 using computational and in vitro methods, identifying key residues and structural changes involved in pH-dependent activation.

The study shows that β-arrestin signaling bias is spatiotemporally determined by ligand dissociation rate and G protein activity at endosomes, not receptor conformation.

This study presents cryo-EM structures of SUCNR1-Gi complexes bound to succinate and epoxysuccinate, revealing key residues and structural changes involved in agonist binding and activation.

This study investigates how disease-associated mutations in G protein subunits affect nucleotide interactions using spectroscopic and computational methods, revealing distinct structural and functional changes.

This study reports the cryo-EM structure of the QRFP-GPR103-Gq complex, revealing unique binding mechanisms and insights into RF-amide peptide recognition.

This paper introduces OptoIso, a photo-labile ligand that selectively activates βAR signaling at the cell surface or endomembranes using blue light, enabling precise study of its role in cardiac pathology.

The paper develops a kinetic model to understand GPCR desensitization by integrating biochemical steps from ligand binding to receptor internalization, identifying three downregulation regimes based on phosphorylation, dephosphorylation, and beta-arrestin levels.

This study determines the cryo-EM structure of QRFPR bound to 26RFa, revealing the recognition mechanism and aiding drug design for obesity and diabetes.

The paper describes a method to create highly biased agonists for GPCRs by tethering a peptide ligand to a nanobody, achieving pathway selectivity without altering the core ligand structure.

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 shows that internalized beta2-Adrenergic Receptors inhibit PLCε signaling at the Golgi, reducing cardiac hypertrophy by blocking PKD and HDAC5 phosphorylation.

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 develops nanobody antagonists against the AT1R receptor, showing they can selectively bind and modulate the receptor with tunable ligand selectivity.

This study uses Bayesian network modeling to identify cooperative GPCR:G protein interactions and their allosteric effects, revealing subnetworks that contribute to G protein coupling selectivity.

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