Receptor Mechanisms and Signaling

The paper introduces synthetic GPCRs that can be programmed to control cell behavior in response to specific antigens, using modular design for versatile applications.

This study uses cryo-EM and single-molecule FRET to show conformational coupling between the extracellular and transmembrane domains of an aGPCR, revealing how ECR dynamics influence receptor function.

This study uses molecular dynamics and network analysis to investigate the allosteric activation mechanisms of the human TAS2R46 receptor under different conditions.

This study presents cryo-EM structures of MCHR1 in active and inactive states, revealing ligand recognition and activation mechanisms to aid drug development.

This study examines the pharmacological properties of mGlu receptor homodimers and heterodimers, finding unique signaling responses to ligands that challenge generalizable rules of dimeric interactions.

This study identifies a non-canonical mechanism of GPCR activation where agonists directly rearrange an intracellular loop to regulate signaling, with implications for drug design.

This study predicts ligand efficacy in the mu-opioid receptor using dynamic analysis and machine learning, showing dynamics are critical for accurate predictions.

This study identifies how arrestin2 interacts with clathrin and AP2 during CCR5 endocytosis, showing that AP2 binding depends on arrestin2 activation and phosphorylation levels.

The paper uses single-molecule imaging and molecular dynamics simulations to study early MET receptor activation in situ, revealing structural dynamics and a refined dimer model.

This study investigates dopamine receptor-ligand interactions using molecular modeling, revealing binding modes and stability of agonists and antagonists at D1R and D5R.

This study compares the potency, dissociation kinetics, and naloxone antagonism of fentanyls and nitazenes at the μ opioid receptor, finding that slowly dissociating agonists are more resistant to naloxone.

This study shows that FgSte2 and FgSte3 GPCRs in F. graminearum form heterodimers in response to peroxidase and HRP-derived ligands, using bioluminescence resonance energy transfer and affinity pulldown.

This study uses molecular dynamics simulations to show that the protonation state of GLU2837.39 in CCR5 affects its conformational changes when bound to GP120 or MRV.

This study uses HDX-MS to analyze structural dynamics of tβ1AR with different ligands, revealing ICL1 dynamics linked to GPCR activation and drug modality.

This paper describes a nanobody antagonist of the μ-opioid receptor, revealing its structural basis and designing peptide analogues with antagonistic activity.

This study determines the cryo-EM structures of KSHV-GPCR in complex with Gi and CXCL1, revealing structural mechanisms of constitutive activation and ligand binding.

The paper identifies lipid ligands that regulate Gsα-stimulated adenylyl cyclase activities through membrane anchors, revealing a new class of receptors with dual signaling functions.

This paper develops spatially restricted antagonists to selectively inhibit β1AR signaling at the plasma membrane versus intracellular compartments, revealing compartment-specific effects on downstream signaling.

This study uses cryoEM to reveal structural details of CXCR4 activation by CXCL12 and its oligomerization, showing new modes of GPCR regulation.

This study investigates how RAMP2 and RAMP3 modulate PTH1R function and signaling, showing RAMP2 enhances responses while RAMP3 reduces them, suggesting potential for targeted therapies.

The paper compares FPR1 and FPR2 signaling profiles using agonists, finding shared core signatures and low activity ratios for FPR2 agonists, challenging assumptions about receptor-specific inflammatory profiles.

This study shows positive allosteric modulators stabilize the GPCR-G protein ternary complex, enhancing signaling when nucleotides are present.

This study uses molecular dynamics simulations to reveal a pseudo-active state in the A2A receptor, providing insights into its activation mechanism and signaling pathways.

This study investigates how PIP2 binding to the C-domain of β-arrestin-2 induces conformational changes leading to its activation.

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.