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Chisae Nagiri and Wataru Shihoya report the crystal structure of the human endothelin receptor ET_B in complex with an ET_B antagonist IRL2500, suggesting different binding modes between IRL2500 and endothelin-1, ET_B’s endogenous ligand. This study provides structural insights into the specificity of ET_B interaction with its ligands.

Cryo-EM structures reveal how the lasso peptide binds the ET_B receptor, blocking its activation via key hydrophobic interactions. These findings advance lasso peptides as potential drugs for hard-to-treat cancers and GPCR-targeting therapies.

Cryo-EM structure of the human PAC1R receptor bound to its neuropeptide ligand PACAP and to an engineered G_s complex reveals the mode of PACAP recognition and suggests functional diversity of the extracellular domains in class B GPCRs.

The X-ray crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1.

Channelrhodopsins are light-gated ion channels for optogenetics. Here, authors report the 2.7 Å cryo-EM structure of a blue-shifted channelrhodopsin from Klebsormidium nitens, revealing a 6-s-cis retinal configuration and unique C-terminal modulation.

Signalling through the endothelin receptor ET_B, a class A GPCR, induces nitric oxide-mediated vasorelaxation. Here the authors present the crystal structures of the human ET_B receptor bound to the peptide hormone endothelin-3 and in complex with the ET_B-selective partial agonist IRL1620 and discuss mechanistic implications for receptor activation.

Description of the cryo-EM structures of the parathyroid hormone type 1 receptor associated with G_q reveals two distinct extracellular conformations with N-glycans stabilizing a ligand-tilted conformation.

Uncultured open-ocean Asgard archaea can harvest light energy using rhodopsins and diverse hydroxylated carotenoid antennas.

CXCR3 and CXCR7 are chemokine receptors involved in cellular migration in physiological and pathophysiological context. Here, the authors present cryo-EM structures of CXCR3 in complex with small molecule agonists and discover their dual-agonism at CXCR7.

Adenosine A₃ receptor (A₃R) plays important roles in neurons, heart, and immune cells, and is often overexpressed in tumors. Oshima et al. identify tRNA-derived i⁶A as an A₃R-selective ligand and use cryo-EM to reveal A₃R’s selectivity and activation mechanisms.

GPR103, a GPCR activated by pyroglutamylated RF-amide peptide QRFP, has various physiological functions, such as energy metabolism and appetite regulation. Here, the authors determined the cryoEM structure of the QRFP26- GPR103-Gq complex, revealing its peptide recognition mechanism.

Xanthorhodopsins with carotenoid antennas are found to be widespread in cyanobacteria and adapted to extreme polar environments by modulating light-harvesting efficiency under prolonged low light intensities and spectral shifts.

GPR34 is a GPCR which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative endogenous ligand. Here, authors report two cryo-EM structures of human GPR34-Gi complex with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or its derivative M1.

Light energy transfer from abundant hydroxylated carotenoids to the retinal moiety of widespread light-driven proton pumps is detected.

LPA₁ is one of the GPCRs that are drug targets for various diseases. Here the authors report a cryo-EM structure of the active human LPA₁-G_i complex bound to an LPA analog with more potent activity against LPA₁ and clarified the ligand recognition mechanism.

A cryo-EM structure of the active human melatonin receptor in complex with G_i reveals conformational changes upon activation and the molecular basis for G-protein selectivity.

Rhodopsin phosphodiesterase (Rh-PDE) hydrolyzes both cAMP and cGMP in a light-dependent manner. Structural and functional analyses of the Rh-PDE from Salpingoeca rosetta reveal unusual rhodopsin topology comprising 8 transmembrane helices (TMs) and suggest that TM0 plays a crucial role in the enzymatic photoactivity.

Crystal structures of human endothelin ET_B receptor bound to bosentan and to ET_B-selective derivative provide insight into the basis of antagonism by these drugs.

This study presents cryo-EM structures of H₄R–G_i and H₁R–G_i/G_s complexes, revealing distinct histamine recognition, activation mechanisms, and a critical determinant of G protein selectivity in H₁R and H₄R.

A crystal structure of Thermoplasmatales archaeon heliorhodopsin at 2.4 Å resolution shows that it adopts a similar fold to that of type I rhodopsin—despite the low sequence identity—but there are also several marked differences that provide insights into heliorhodopsin function.

A cryo-electron microscopy structure for the human (lysophosphatidic acid receptor 1) LPA1-Gi complex bound to a nonlipid agonist provides mechanistic insights into how nonlipid agonists activate LPA1.