Receptor Mechanisms and Signaling

A pan-positive allosteric modulator that mediates sustainable GPCR activation

This paper identifies atazanavir as a pan-positive allosteric modulator that activates multiple Family A GPCRs and sustains G protein signaling through non-canonical mechanisms.

A GPCR-G protein-β-arrestin megacomplex induced by an allosteric modulator

This study determines the structure of a GPCR-G protein-β-arrestin complex stabilized by an allosteric modulator, showing a novel binding mode that allows coexistence with G protein signaling.

De novo design of miniprotein agonists and antagonists targeting G protein-coupled receptors

This paper presents computational methods for designing GPCR-binding miniproteins and validates them through high-throughput screening, producing agonists and antagonists for multiple GPCRs.

Structure and dynamics determine G protein coupling specificity at a class A GPCR

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

Oxysterol accumulation in aging cells alters GPCR signalling

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

Characterization and targeting of the endosomal signaling of the gastrin releasing peptide receptor in pruritus.

This study investigates GRPR endosomal signaling in pruritus and shows that endosomal targeting of GRPR antagonists is more effective in blocking itch sensation.

Post-translational modifications orchestrate the intrinsic signaling bias of orphan receptor GPR52

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

The G protein inhibitor YM-254890 is an allosteric glue

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'.

GPR27 mediates adrenergic ligands-induced transinhibition of EGFR

This study shows GPR27 mediates adrenergic ligand-induced transinhibition of EGFR through dephosphorylation of c-Src and EGFR, independent of G-proteins and β-arrestins.

Rare variant in intracellular loop-2 of the ghrelin receptor reveals novel mechanisms of GPCR biased signaling and trafficking

The paper characterizes a rare GHSR variant, L149P, revealing novel roles of intracellular loop-2 in GPCR biased signaling, lipid modulation, and trafficking through experimental and computational methods.

Nanobody-based conjugates targeting small molecule-binding GPCRs and exhibiting logic-gated signaling

This paper develops bitopic conjugates targeting GPCRs that enable logic-gated signaling by activating receptor pairs.

Revealing Water-Mediated Activation Mechanisms in the Beta 1-Adrenergic Receptor via OneOPES-Enhanced Free Energy Landscapes

This study uses OneOPES to analyze the activation mechanism of ADRB1, revealing water-mediated interactions and structural changes important for receptor activation.

Relating GPCR domains with functionality: receptor helix-bundle and C-terminus differentially influence GRK-specific functions and β-arrestin-mediated regulation

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

Endocytosis drives active cAMP signal discrimination among natively co-expressed GPCRs

The paper shows that endocytosis differentiates cAMP signaling profiles of co-expressed GPCRs by shaping spatiotemporal cAMP dynamics.

A single domain intrabody as a novel tool to bias the subcellular trafficking of the follicle-stimulating hormone receptor

The paper describes a single domain intrabody, iPRC2, that biases the subcellular trafficking of the follicle-stimulating hormone receptor (FSHR) by rerouting it to early endosomes, reducing its surface recycling and cAMP production.

Evolutionary Dynamics of Lineage-Specific Class-A GPCR Subsets Reveal Widespread Chemosensory Roles and Adaptations in Lophotrochozoa

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

Helix-8 and Carboxyl Terminal Tail Regulation of Proteinase Activated Receptor-4 (PAR4) signalling

This study investigates how the 8th-helix and carboxyl terminal tail of PAR4 regulate signaling by affecting G protein activation, β-arrestin recruitment, and interactions with regulatory proteins.

Cryo-EM reveals a new allosteric binding site at the M5 mAChR

The paper presents a cryo-EM structure of the M5 mAChR with a novel allosteric binding site identified through mutagenesis, pharmacology, and simulations.

Mechanisms of peptide agonist dissociation and deactivation of adhesion G-protein-coupled receptors

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

Structural Diversity and Dynamics of Metabotropic Glutamate Receptor/Beta-Arrestin Coupling

This study investigates the structural and dynamic diversity of metabotropic glutamate receptor/beta-arrestin coupling using biophysical and structural methods, revealing new coupling stoichiometries and interaction mechanisms.

The physiological impact of an N-terminal Halo-tag on GIPR function in mice

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.

Molecular Basis of PAC1R Allosteric Modulation with Lipids in Membranes

This study identifies lipid binding sites on PAC1R using simulations, showing cholesterol and GM3 interact with the receptor in multiple domains, potentially influencing its activation.

Molecular insights into the modulation of the 5HT2A receptor by serotonin, psilocin, and the G protein subunit Gqalpha

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

Ligand Binding Effects on Activation of Type-2 Angiotensin II Receptor

This study uses molecular dynamics simulations to show how Ang II and Ang 1-7 ligands differentially affect AGTR2 activation by stabilizing or modulating receptor states through specific interactions.

An arginine switch drives the stepwise activation of β-arrestin

This study identifies an arginine switch mechanism that drives the stepwise activation of β-arrestin through conformational changes induced by GPCR interactions.

Evidencing the role of a conserved polar signaling channel in the activation mechanism of the u-opioid receptor

The paper investigates the role of a conserved polar signaling channel in the activation of the mu-opioid receptor through mutations and simulations, showing its critical role in agonist binding and G protein stimulation.

G protein-coupled receptor 17 inhibits glucagon-like peptide-1 secretion via a Gi/o-dependent mechanism in enteroendocrine cells

This study investigates how GPR17 inhibits GLP-1 secretion in enteroendocrine cells through Gi/o-dependent signaling, using pharmacological and genetic approaches.

AlphaFold prediction and analysis of Adhesion-family G protein coupled receptor (aGPCR) structures.

The paper uses AlphaFold to predict and analyze 3D structures of aGPCRs in active and inactive states, revealing insights into their activation mechanisms and conformational changes.

Identification and Pharmacological Characterization of Multiple Allosteric Binding Sites on the Free Fatty Acid 1 Receptor

The paper identifies and characterizes multiple allosteric binding sites on FFA1, showing cooperativity between agonists and implications for therapeutic development.

Synthetic G protein-coupled receptors for programmable sensing and control of cell behavior

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