8xjn
Cloprosetnol bound Thromboxane A2 receptor-Gq Protein Complex
Structural highlights
FunctionGBB1_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.[1] Publication Abstract from PubMedProstaglandin F(2alpha) (PGF(2alpha)) and thromboxane A(2) (TXA(2)) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through activating PGF(2alpha) receptor (FP) and TXA(2) receptor (TP). Ligands targeting FP and TP have demonstrated efficacy in treating conditions like glaucoma and cardiovascular diseases in humans, as well as reproductive-related diseases in animals. Here, we present five cryoelectron microscopy structures illustrating FP and TP in complex with G(q) and bound to PGF(2alpha) (endogenous ligand), latanoprost acid (a clinical drug), and two other synthetic agonists. Combined with mutational and functional studies, these structures reveal not only structural features for the specific recognition of endogenous ligands and attainment of receptor selectivity of FP and TP but also the common mechanisms of receptor activation and G(q) protein coupling. The findings may enrich our knowledge of ligand recognition and signal transduction of the prostanoid receptor family and facilitate rational ligand design toward these two receptors. Structural basis for ligand recognition and activation of the prostanoid receptors.,Li X, Zhang X, Wen X, Zhang D, Qu C, Miao X, Zhang W, Zhang R, Liu G, Xiao P, Sun JP, Gong W Cell Rep. 2024 Mar 26;43(3):113893. doi: 10.1016/j.celrep.2024.113893. Epub 2024 , Mar 5. PMID:38446662[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
