9jfk

Cryo-EM structure of [Pen5]-urotensin (4-11)-bounded human Urotensin receptor (UTS2R)-Gq complex

spinqualitylabelsall models 9jfk, resolution 3.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9jfk is a 6 chain structure with sequence from Homo sapiens, Lama glama and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.23Å Ligands: CHO, LE1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Publication Abstract from PubMed Urotensin-II (U-II) is a potent vasoconstrictor peptide that interacts with the human urotensin-II receptor (UTR), a class A G protein-coupled receptor (GPCR) that primarily couples with G(q) proteins. In this study, we present the cryo-electron microscopy structure of the miniG(q)-coupled UTR bound to the potent UTR agonist P5U, providing insights into unique ligand recognition and activation mechanisms. Unlike typical linear peptides, the cyclic structure of P5U engages the receptor's transmembrane domains through key side chain interactions involving residues F6, W7, K8, and Y9, which are crucial for receptor activation. Comparative analysis with somatostatin receptors (SSTRs) reveals distinct ligand specificity, driven by variations in side chain composition. Notably, we identify F274(6.51) as the toggle switch residue in UTR, in contrast to the classical W(6.48) seen in other GPCRs. Our findings elucidate the structural basis for UTR's G(q) coupling specificity, highlighting unique Galpha(q) interactions. This study advances the understanding of U-II signaling and offers a foundation for developing selective UTR modulators, with potential therapeutic implications for cardiovascular diseases linked to dysregulated U-II activity. Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor.,Gao T, You C, Cao Y, Xu X, Yuan Q, Shen S, Xu HE, Duan J J Biol Chem. 2025 Nov;301(11):110794. doi: 10.1016/j.jbc.2025.110794. Epub 2025 , Oct 6. PMID:41062066 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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