8IUM

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

8IUM の概要

• エントリーDOI: 10.2210/pdb8ium/pdb
• EMDBエントリー: 35726
• 分子名称: G subunit alpha (q), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Antibody fragment scFv16, ... (7 entities in total)
• 機能のキーワード: gpcr, ptgfr, tfpa, gq, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 170238.33

構造登録者

Wu, C.,Xu, Y.,Xu, H.E. (登録日: 2023-03-24, 公開日: 2023-07-12, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.14 Å)