Receptor Mechanisms and Signaling

This study uses mass spectrometry to show how MRAP and antagonists affect MC2R conformations and dynamics.

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.

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 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.

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

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

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.

This study investigates how receptor phosphorylation and membrane lipids cooperatively control arrestin activation, identifying key phospho-motifs and lipid interactions.

The paper investigates the slow dissociation of nitazenes from the μ-opioid receptor, showing it contributes to overdose reversal challenges and provides structural insights into the mechanism.

This study uses computational methods to analyze how different peptide ligands interact with the human urotensin II receptor, revealing structural differences in receptor activation.

This paper introduces a pipeline combining AI-assisted construct screening and de novo protein design to rapidly determine high-resolution GPCR structures, validated on multiple receptors.

This study identifies a novel mechanism where Gq/11 and G12/13 activation causes SH2 domain-containing proteins to translocate from the plasma membrane to the nucleus, reducing RTK signaling activity.

The paper identifies M1 muscarinic and H3 histamine receptors as targets for OPC differentiation and analyzes their ligand interactions using computational methods.

This paper introduces TQ1 probes to map non-canonical cholesterol-binding sites on the M1 muscarinic receptor, showing improved quenching and binding specificity compared to Dabcyl.

This study examines how the A338V mutation in GPR183 affects receptor function, showing preserved G protein activation but impaired GRK2 and β-arrestin2 recruitment.

This study shows sodium ions regulate GPCR activation by altering allosteric coupling networks and hydration patterns in the dopamine D2 receptor.