Receptor Mechanisms and Signaling

Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer

This study develops and validates BRET-based assays to detect constitutive and ligand-dependent Gi-directed activity in GiPCRs, revealing novel regulatory mechanisms of Smoothened.

Implications of gen(om)e duplications on the expansion and evolution of the GPCR signalling pathway

The paper analyzes the duplication history of GPCR signalling pathway components across evolution, finding distinct duplication frequencies and evolutionary ages among pathway elements.

Unique Pharmacology of mGluR homo- and heterodimers

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.

A non-canonical mechanism of GPCR activation

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.

A high-resolution analysis of arrestin2 interactions responsible for CCR5 endocytosis

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

Structural Basis of GPCR-G Protein Pre-coupling and Activation: Insights from CCR1-Gi Complex

The paper solves the cryo-EM structure of CCR1-Gi complex in pre-coupled state, revealing molecular mechanism of GPCR-G protein activation and highlighting conserved pre-coupling in chemokine receptors.

Potency, dissociation kinetics and reversibility of fentanyls and nitazenes by naloxone at the μ opioid receptor

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.

Structural Basis of μ-Opioid Receptor-Targeting by a Nanobody Antagonist

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

A new class of receptors: Lipids regulate mammalian Gsα-stimulated adenylyl cyclase activities via their membrane anchors

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.

Cryo-EM structures of human GPR155 elucidate its regulatory and transport mechanisms

This study presents cryo-EM structures of human GPR155, revealing its transporter and GPCR domains' conformations and cholesterol-dependent dimerization.

Structural basis for the access and binding of resolvin D1 (RvD1) to formyl peptide receptor 2 (FPR2/ALX), a class A GPCR

This study investigates how RvD1 accesses and binds to FPR2/ALXR using molecular dynamics and metadynamics simulations, revealing structural insights and potential therapeutic implications.

Osteocalcin binds to the GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling

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.

G protein-Coupled Receptor Associated Sorting ProteinGASP1 mediated trafficking of the Glucagon Like Peptide-1Receptor contributes to the development of tolerance toincretin drugs

This study shows that GASP1-mediated GLP-1R trafficking contributes to tolerance to incretin drugs, suggesting a strategy to prevent tolerance by biasing drug engagement toward G protein signaling.

Molecular mechanism of the endothelin receptor type B interactions with Gs, Gi, and Gq

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.

Discovery and pharmacological characterization of nanobodies acting as potent positive allosteric modulators of the calcium-sensing receptor

This study identifies and characterizes nanobodies that act as potent positive allosteric modulators of the calcium-sensing receptor, offering new tools for research and potential therapeutic applications.

Elucidating the activation mechanism of the proton-sensing GPR68 receptor

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.

AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration

This study introduces an optogenetic GDI tool to induce Gβγ signaling independently of GPCRs and demonstrates its ability to trigger macrophage migration.

Endogenous Promotor-Driven Split Nanoluciferase Biosensor for Assessing G Protein Recruitment

The paper uses CRISPR/Cas9 to tag native β-adrenoceptors and a minimal Gs protein with split Nanoluciferase under endogenous promoters in HEK293T cells, enabling selective-ligand characterization without overexpression.

Biosensor imaging of G protein mediated Signaling Pathways Activated Immediately Downstream of CaSR

The paper uses biosensors to study CaSR-mediated signaling pathways in HEK-293 cells, showing activation of Gq and Gi proteins and their effects on intracellular calcium and cAMP levels.

Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors

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

The landscape of cancer rewired GPCR signaling axes

The paper analyzes GPCR signaling dysregulation in cancer transcriptomics data to identify therapeutic targets and survival-associated signaling axes.

Structural Insights into the Unexpected Agonism of Tetracyclic Antidepressants at Serotonin Receptors 5-HT1eR and 5-HT1FR

The paper investigates the agonist activity of tetracyclic antidepressants at 5-HT1eR and 5-HT1FR, revealing unique binding poses and receptor-specific mechanisms.

Physiological bias governs neutrophil inflammatory threat perception

The paper shows that the cellular environment significantly affects GPCR signaling, leading to physiological bias in neutrophils that impacts drug efficacy.

Essential Dynamics of CB1 Receptor-Agonist Complexes: Implications for Signalling Bias

This study uses molecular dynamics to show that different CB1 receptor agonists induce distinct conformations leading to biased signalling through differential coupling to G proteins and beta-arrestins.

Molecular insights into the atypical activation mechanism of GPR156 in maintaining auditory function

This study reveals the constitutive activity and dimerization mechanism of GPR156, explaining its role in auditory function through cryo-EM structures and functional analysis.

Exploring human rare disease variants from a multidimensional perspective illuminates receptor - G protein coupling diversity

This study investigates rare disease variants in Gs, a G protein, using multidimensional approaches to reveal how mutations affect receptor-Gs coupling and signaling defects.

Larixol is not an inhibitor of Gαi containing G proteins and lacks effect on signaling mediated by human neutrophil expressed formyl peptide receptors

This study shows that Larixol does not inhibit Gi or Gq containing G proteins in human neutrophils, contradicting previous claims about its inhibitory effects on FPR1 and related receptors.

Shedding Light on the D1-Like Receptors: A Fluorescence-Based Toolbox for Visualization of the D1 and D5 Receptors

The paper introduces a fluorescent ligand for visualizing D1 and D5 dopamine receptors, showing high affinity and selectivity with applications in fluorescence microscopy.

Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors

This study uses deep learning and simulations to reveal dynamic allostery mechanisms in GPCRs, showing modulators restrict conformational space and enhance selectivity.

Modeling stereospecific drug interactions with beta-adrenergic receptors

The paper develops structural models of beta-1 and beta-2 adrenergic receptors with beta-blockers using RosettaLigand and MD simulations, identifying structural features and stability but not clearly distinguishing stereospecific drug preferences.