8XJL

PGF2-alpha bound Prostaglandin F2-alpha receptor-Gq Protein Complex

Summary for 8XJL

• Entry DOI: 10.2210/pdb8xjl/pdb
• EMDB information: 38400
• Descriptor: Engineered miniGq, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: cryo-em, complex, signaling protein, membrane protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 5
• Total formula weight: 169172.63

Authors

Zhang, X.,Li, X.,Liu, G.,Gong, W. (deposition date: 2023-12-21, release date: 2024-02-28, Last modification date: 2024-11-13)

Primary citation

Li, X.,Zhang, X.,Wen, X.,Zhang, D.,Qu, C.,Miao, X.,Zhang, W.,Zhang, R.,Liu, G.,Xiao, P.,Sun, J.P.,Gong, W.
Structural basis for ligand recognition and activation of the prostanoid receptors.
Cell Rep, 43:113893-113893, 2024

PubMed Abstract: Prostaglandin F (PGF) and thromboxane A (TXA) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through activating PGF receptor (FP) and TXA 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 and bound to PGF (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 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.

PubMed: 38446662
DOI: 10.1016/j.celrep.2024.113893

Experimental method

ELECTRON MICROSCOPY (2.77 Å)