8iq4 | pdb_00008iq4

Cryo-EM structure of Carboprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex

spinqualitylabelsall models 8iq4, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8iq4 is a 5 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.7Å Ligands: 87Q Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PF2R_HUMAN Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum (By similarity). Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and isoform 5 are proposed to be a receptor for prostamides including the synthetic analog bimatoprost. Publication Abstract from PubMed Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F(2alpha) and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 A and 3.2 A resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs. Structures of human prostaglandin F(2alpha) receptor reveal the mechanism of ligand and G protein selectivity.,Lv X, Gao K, Nie J, Zhang X, Zhang S, Ren Y, Sun X, Li Q, Huang J, Liu L, Zhang X, Zhang W, Liu X Nat Commun. 2023 Dec 8;14(1):8136. doi: 10.1038/s41467-023-43922-8. PMID:38065938 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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