| Structural highlights
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liang Y, Woodward DF, Guzman VM, Li C, Scott DF, Wang JW, Wheeler LA, Garst ME, Landsverk K, Sachs G, Krauss AH, Cornell C, Martos J, Pettit S, Fliri H. Identification and pharmacological characterization of the prostaglandin FP receptor and FP receptor variant complexes. Br J Pharmacol. 2008 Jul;154(5):1079-93. PMID:18587449 doi:10.1038/bjp.2008.142
- ↑ 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. Structures of human prostaglandin F(2α) receptor reveal the mechanism of ligand and G protein selectivity. Nat Commun. 2023 Dec 8;14(1):8136. PMID:38065938 doi:10.1038/s41467-023-43922-8
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