Receptor Mechanisms and Signaling

This study shows that increasing μ-opioid receptor density promotes trafficking via GRK2/3 and β-arrestin interactions, while class B GPCRs block trafficking by sequestering β-arrestin.

The paper identifies a conserved hydrophobic interaction that mediates competition between GPCR transducers and regulators.

The paper uses machine learning and simulations to show that distant residue interactions in the G protein core influence GPCR selectivity and can be engineered to change signaling preferences.

This study discovers μ-opioid receptor positive allosteric modulators (PAMs) and investigates their dynamic mechanism of action to enhance opioid agonist activity while reducing side effects.

The paper reveals how beta-arrestin 1 activates Src kinase via two distinct SH3 domain interactions, using cryo-EM to show structural mechanisms of beta-arrestin-mediated signaling.

This study identifies shared molecular mechanisms by which MRAP2 regulates GPCR signaling and shows that obesity-associated variants disrupt these mechanisms.

This study investigates how GPCRs regulate G protein activity on endosomes using conformational biosensors, finding that endocytosis is required for active Gs production on endosomes.

This study investigates FFA2R allosterism across cell models, showing pathway-selective modulation and highlighting Ca2+ mobilization and ROS as therapeutic readouts.

The paper presents a cryo-EM structure of the dopamine D2 receptor bound to a non-basic ligand, revealing structural dynamics and binding energy landscapes that explain subtype selectivity.

The paper uses molecular simulations to show that address-domain engagement before message-domain binding increases the success rate of β-endorphin binding to the μ-opioid receptor.

The paper identifies a constitutively active mutant of the dopamine D2 receptor using computational methods and experimental validation.

This paper introduces novel GαGTP sensors to measure endogenous G protein signaling dynamics, revealing subtype-dependent dissociation and subcellular regulation.

This study uses an optogenetic platform to activate a GPCR at different intracellular membranes, showing location-dependent transcriptional responses.

The paper designs rigid protein fiducials using generative design and deep learning to enable cryoEM visualization of GPCR conformational states, validated with four GPCR inactive structures.

Hyaline predicts GPCR activation states from 3D structures using geometric deep learning, achieving high accuracy and outperforming sequence-only models.

This study investigates how different detergents affect the stability and ligand binding of neurotensin receptor 1, revealing a trade-off between structural stabilization and conformational flexibility.

This study uses NMR and MD simulations to analyze conformational entropy changes in GPCRs, showing how dynamic fluctuations influence allosteric signaling and receptor function.

The study shows the ADGRG6/GPR126 Stachel peptide is intrinsically disordered in solution, with limited helical conformations detected by biophysical experiments.

This study identifies sequence constraints that predispose Class D GPCRs to an atypical activation mechanism involving TM7 displacement and TM6 inward movement.

This paper develops an engineered nanobody inhibitor to control opioid receptor function with subcellular precision and demonstrates its effectiveness in vivo.

This paper investigates how superagonists at the μ-opioid receptor are less sensitive to Na+ ions compared to standard agonists, suggesting a conformational induction mechanism.

This study reveals an unconventional activation mechanism of the atypical GPCR ACKR3 using engineered nanobodies and cryo-EM, showing that extracellular pocket volume changes, not microswitch conformational shifts, drive receptor activity.

The paper uses molecular dynamics simulations and FRET assays to study lipid interactions with class B1 GPCRs, revealing state-dependent and conserved lipid binding patterns.

This study compares the membrane-binding properties of arrestin-2 and arrestin-3 using biophysical and cell-based methods, revealing distinct lipid interaction mechanisms and activation dynamics.

This study uses MD simulations to show that Class B1 GPCRs share a common activation mechanism involving an intermediate state with outward movement of helix 6, but exhibit clade-specific residue-level differences.

This paper describes a pepducin derived from NTS1 that acts as a biased allosteric modulator, preferentially activating G proteins over β-arrestin and inhibiting receptor internalization.

The paper shows that biased ligands of the AT1R receptor stabilize different conformations that differentially modulate β-arrestin interactions, affecting signaling and desensitization.

This study uses a split-YFP BiFC assay to show that severe GNAO1 mutations impair GPCR disengagement, while milder mutants show near-normal receptor internalization.

This study uses single-molecule imaging to show how agonist-specific dynamics in structured and disordered regions of the 2AAR regulate signaling and function.

This study uses Pep-GaMD simulations to reveal how a tethered agonist transitions from a β-strand to a U-shaped helical configuration upon binding to ADGRD1.