Receptor Mechanisms and Signaling

Fluorescent Tools for Imaging and Ligand Screening of Dopamine D2-Like Receptors

This paper describes the synthesis and characterization of fluorescent ligands for imaging and ligand screening of dopamine D2-like receptors, showing high affinity and selectivity.

Cryo-EM structure of cell-free synthesized human histamine H2 receptor coupled to heterotrimeric Gs protein in lipid nanodisc environment

The paper presents the cryo-EM structure of the human histamine H2 receptor complexed with Gs protein in lipid nanodiscs, revealing insights into ligand binding and G protein coupling mechanisms.

Molecular recognition of an aversive odorant by the murine trace amine-associated receptor TAAR7f

The paper determines the cryo-EM structure of mTAAR7f bound to DMCH, revealing its unique binding site and activation mechanism distinct from ORs.

Constitutive Activation and Oncogenicity Are Mediated by Loss of Helical Structure at the Cytosolic Boundary of the Thrombopoietin Receptor

The paper investigates how mutations in the thrombopoietin receptor (TpoR) affect its activation and oncogenicity by altering the helical structure at the cytosolic boundary of the transmembrane domain.

Differentiating Agonists and Competitive Antagonists of the Serotonin Type 3A (5-HT3A) Receptor

The paper differentiates agonists and competitive antagonists of the 5-HT3A receptor using Monte Carlo simulations and linear response theory.

Gαs slow conformational transition upon GTP binding and a novel Gαs regulator

The paper characterizes the conformational changes in the Gαs protein upon GTP binding and identifies a novel regulator, MAGE D2, using a Bayesian integrative modeling approach.

Arrestin-3 agonism at D3 dopamine receptors defines a subclass of second generation antipsychotics that promotes drug tolerance

This study identifies some second generation antipsychotics (SGAs) as arrestin-3 agonists at D3 dopamine receptors, showing that chronic use leads to receptor degradation and altered drug efficacy.

Structural basis of peptide recognition and activation of endothelin receptors

The paper presents cryo-EM structures of endothelin receptors bound to ligands, revealing their recognition mode and activation mechanism.

Modeling the Orthosteric Binding Site of the G Protein-Coupled Odorant Receptor OR5K1

The paper models the orthosteric binding site of the odorant receptor OR5K1 using AI-driven structural data and mutagenesis data to refine ligand binding modes.

Intron retention of an adhesion GPCR generates single transmembrane-helix isoforms to enable 7TM-adhesion GPCR function

The paper shows that intron retention generates single transmembrane-helix isoforms of aGPCRs, enabling mechanosensory function through heteromerization with 7TM subunits.

ADRA2B and HTR1A: An updated study of the biogenic amine receptors reveals novel conserved motifs which play key role in Mental Disorders.

This study investigates conserved motifs in ADRA2B and HTR1A, two biogenic amine receptors, to understand their role in mental disorders through evolutionary and structural analysis.

5-HT1A and 5-HT2B receptor interaction and co-clustering regulates serotonergic neuron excitability

This study investigates the interaction and co-clustering of 5-HT1A and 5-HT2B receptors in serotonergic neurons and shows their functional impact on neuronal excitability.

Endocytic trafficking determines cellular tolerance of presynaptic opioid signaling

This paper identifies endocytic trafficking as a mechanism for presynaptic opioid tolerance, showing that receptor cycling and phosphorylation-dependent endocytosis contribute to tolerance development.

SSB toolkit: from molecular structure to subcellular signaling pathways.

The paper introduces an open-source systems biology toolkit to simulate GPCR signal-transduction pathways using structural data and mathematical models.

GPCRome-wide structural analysis of G-protein-coupling selectivity

The paper analyzes GPCR-G-protein complexes to identify structural determinants of G-protein coupling selectivity, revealing differences in contact patterns and stability between Gs and Gi/o complexes.

Subthreshold serotonin signals combined by the G proteins Gαq and Gαs activate the C. elegans egg-laying muscles

The paper shows that subthreshold serotonin signals via Gq and Gs pathways combine in C. elegans egg-laying muscles to promote egg laying, while individual signals alone are insufficient.

Combined docking and machine learning identifies key molecular determinants of ligand pharmacological activity on β2 adrenoceptor.

The paper uses docking and machine learning to identify molecular interactions that determine agonist or antagonist activity of β2 adrenoceptor ligands.

Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses

The paper introduces DREADD-based GPCR chimeras to study cell type-specific signaling and microglia responses without endogenous ligands.

Extracellular loop 2 of G protein-coupled olfactory receptors is critical for odorant recognition

This study shows that ECL2 in GPCRs is crucial for odorant recognition and promiscuity, enabling virtual screening of ligands with high success.

A unique peptide recognition mechanism by the human relaxin family peptide receptor 4 (RXFP4)

The paper reports cryo-EM structures of RXFP4-Gi complexes with INSL5 and agonists, revealing a unique peptide-binding mechanism and subtype selectivity determinants.

Proteins with multiple G protein-coupled receptor domains

The paper identifies 57 proteins with multiple GPCR domains, analyzes their structures, and suggests new possibilities in GPCR evolution and signal transduction.

The N terminus of adhesion G protein-coupled receptor GPR126/ADGRG6 as allosteric force integrator

This study identifies the N terminus of GPR126 as an allosteric force integrator that translates ECM binding into intracellular signals through distinct activation modes.

Basis for antibody- and hormone-mediated activation of TSHR in Graves' disease

The paper reports the structures of TSHR activated by TSH and an autoantibody, revealing a universal activation mechanism and the role of cholesterol in TSHR localization.

Structural insights into G protein activation by D1 dopamine receptor

The paper presents cryo-EM structures of D1 dopamine receptor-Gs complexes in different nucleotide states, revealing conformational changes and a sequence motif that determines G protein selectivity.

Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols

This study engineers yeast to produce cholesterol, enabling functional expression of human opioid and other GPCRs, creating biosensors with measurable agonist responses and antagonist inhibition.

Structure-guided optimization of light-activated chimeric G-protein coupled receptors

This paper demonstrates structure-guided optimization of light-activated chimeric GPCRs to enhance their function and spectral tuning capabilities.

Structural basis of peptidomimetic agonism revealed by small molecule GLP-1R agonists Boc5 and WB4-24

This paper reports cryo-EM structures of small molecule GLP-1R agonists Boc5 and WB4-24, revealing a novel binding pocket and mechanism for peptidomimetic agonism.

A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2

This study reports the cryo-EM structure of the human VIP2R bound to PACAP27 and Gs, revealing a unique N-terminal helix conformation that stabilizes the ligand-receptor interface.

Profiling the proximal proteome of the mu opioid receptor identifies novel regulators of receptor signaling and trafficking

The paper identifies novel regulators of mu opioid receptor signaling and trafficking using proximity labeling and proteomics.

Crystal structure of a constitutive active mutant of adenosine A2A receptor

The paper determines the crystal structure of a constitutive active A2A receptor mutant to elucidate the molecular mechanism of mutation-induced activity.