Receptor Mechanisms and Signaling

This study uses simulations to show that buprenorphine restricts the conformational states of the μ-opioid receptor compared to endomorphin-1, affecting signaling bias and efficacy.

This study presents cryo-EM structures of RXFP1 bound to relaxin-2 and AZD5462, revealing distinct activation mechanisms for protein and small-molecule agonists.

The paper develops a transformer-based autoencoder framework to analyze conformational landscapes of β-arrestin 1 tail in basal and active states, revealing modular organization and state-dependent dynamics.

This paper introduces SynPARs, synthetic protease-activated receptors that enable cells to sense and respond to protease activity, demonstrating their use in counteracting hyperalgesia in mice.

The paper shows that GPCRs can distinguish neuromodulatory inputs through temporal coding, despite sharing a common transducer pathway.

The paper identifies subtype-specific conserved residues in G protein subtypes that modulate Gβγ coupling, showing conservation does not guarantee functional equivalence.

This study determines the cryo-EM structures of OXGR1 bound to metabolites, revealing conserved mechanisms for metabolite recognition and receptor activation.

This study shows that S-nitrosylation of PKA regulatory subunits by SCAN is required for GPCR-induced PKA activation in heart, brain, and fat tissues.

This study identifies structural features of the A2AR receptor that enable pH sensing without the typical acidic triad, showing mutations can eliminate pH sensitivity while preserving agonist signaling.

This study shows opioid receptors act as proton-gated coincidence detectors, with a conserved aspartic acid residue critical for pH sensing and agonist activation.

The paper identifies GCR1 as the sole GPCR in vascular plants through phylogenetic and bioinformatic analysis, suggesting its role in root hair function.

The paper introduces an off-target-free chemogenetic platform to study GPCR functions, demonstrating its application on the adenosine A2A receptor and showing its generalizability to other class A GPCRs.

This study shows β-arrestin condensates regulate GPCR function through liquid-liquid phase separation, influencing internalization and signaling.

The paper shows that signaling in mGlu1/5 heterodimers is dominated by the mGlu protomer, leading to emergent signaling and allosteric inversion, with implications for drug design.

This paper introduces a quantitative imaging framework to study GPCR oligomerization in living cells, revealing density-dependent monomer-dimer equilibria and apparent affinities for dimerization.

The paper presents two models of the European robin LWO-Gt complex, showing AlphaFold3 predicts an active-state biased Gα subunit, while a template-guided model lacks this bias.

This study identifies two distinct conformational equilibria in arrestin-2 that underlie its pre-activation state in solution.

This study shows that GRKs are essential for ACKR3 endocytosis and chemokine scavenging, while β-arrestins and receptor phosphorylation are not required.

The paper identifies a novel RGS6 isoform, RGS6B, which lacks canonical G protein regulatory effects but exhibits dominant negative actions and stabilizes RGS6 binding partners.

This paper reports the cryo-EM structure of the M4 mAChR bound to MK-97 and acetylcholine, revealing how MK-97's binding mode improves PAM activity through distributed interactions.

This paper introduces a ligand-guided selection method to discover aptamers specific to GPCRs in their native membrane context, showing they bind selectively to cell-surface receptors and induce internalization.

This paper introduces GPCR-CoINPocket v2, a method to detect pharmacological similarities in GPCRs using sequence and ligand interaction data, revealing new relationships and aiding drug discovery.

This study identifies a novel allosteric site on the mu-opioid receptor using cryo-EM and MD simulations, revealing a lipid-sensitive mechanism for positive allosteric modulation.

This study identifies key Y4R residues and discovers selective non-peptide small-molecule agonists through molecular docking, residue replacement, and ultra-large library screening.

The paper reveals how phosphorylation of SMO in the Hedgehog pathway stabilizes a conformation that inhibits PKA-C, providing a structural mechanism for noncanonical GPCR signaling.

This paper presents cryo-EM structures of CCR7 with CCL19 and CCL21, revealing distinct binding modes and dynamic receptor conformations that underlie biased agonism and differential signaling outcomes.

This study identifies an oncogenic TMD mutation in IL-7R that causes ligand-independent signaling and shows that rationally designed transmembrane helices can reverse this effect.

The paper shows that ESM-2 attention maps encode the directional hierarchy of allosteric communication in the adenosine A2A receptor through topological asymmetry.

This study investigates the polypharmacological profiles of xanomeline and its metabolite N-desmethylxanomeline, revealing their agonist and antagonist actions at multiple biogenic amine G protein-coupled receptors.

The paper identifies two regions in the CaSR cytoplasmic domain critical for β-arrestin recruitment, desensitization, and internalization, and shows mutations in these regions contribute to hypocalcemia.