8IUM

Cryo-EM structure of the tafluprost acid-bound human PTGFR-Gq complex

Summary for 8IUM

• Entry DOI: 10.2210/pdb8ium/pdb
• EMDB information: 35726
• Descriptor: G subunit alpha (q), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Antibody fragment scFv16, ... (7 entities in total)
• Functional Keywords: gpcr, ptgfr, tfpa, gq, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 170238.33

Authors

Wu, C.,Xu, Y.,Xu, H.E. (deposition date: 2023-03-24, release date: 2023-07-12, Last modification date: 2024-10-23)

Primary citation

Wu, C.,Xu, Y.,He, Q.,Li, D.,Duan, J.,Li, C.,You, C.,Chen, H.,Fan, W.,Jiang, Y.,Eric Xu, H.
Ligand-induced activation and G protein coupling of prostaglandin F 2 alpha receptor.
Nat Commun, 14:2668-2668, 2023

PubMed Abstract: Prostaglandin F (PGF), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 Å, 2.78 Å, and 3.14 Å. These structures reveal distinct features of FP within the lipid receptor family in terms of ligand binding selectivity, its receptor activation, and G protein coupling mechanisms, including activation in the absence of canonical PIF and ERY motifs and G coupling through direct interactions with receptor transmembrane helix 1 and intracellular loop 1. Together with mutagenesis and functional studies, our structures reveal mechanisms of ligand recognition, receptor activation, and G protein coupling by FP, which could facilitate rational design of FP-targeting drugs.

PubMed: 37160891
DOI: 10.1038/s41467-023-38411-x

Experimental method

ELECTRON MICROSCOPY (3.14 Å)