9GE2

Structure of GPR55 in complex with G13 and synthetic agonist ML184

これはPDB形式変換不可エントリーです。

9GE2 の概要

• エントリーDOI: 10.2210/pdb9ge2/pdb
• EMDBエントリー: 51284
• 分子名称: Guanine nucleotide-binding protein subunit alpha-13, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Single-chain variable fragment ScFv16, ... (9 entities in total)
• 機能のキーワード: g protein-coupled receptor, gpcr, lipid agonist, cholesterol, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 175973.97

構造登録者

Claff, T.,Ebenhoch, R.,Weichert, D. (登録日: 2024-08-06, 公開日: 2025-03-05)

主引用文献

Claff, T.,Ebenhoch, R.,Kley, J.T.,Magarkar, A.,Nar, H.,Weichert, D.
Structural basis for lipid-mediated activation of G protein-coupled receptor GPR55.
Nat Commun, 16:1973-1973, 2025

PubMed Abstract: GPR55 is an orphan G protein-coupled receptor (GPCR) and represents a promising drug target for cancer, inflammation, and metabolic diseases. The endogenous activation of lipid GPCRs can be solely mediated by membrane components and different lipids have been proposed as endogenous activators of GPR55, such as cannabinoids and lysophosphatidylinositols. Here, we determine high-resolution cryo-electron microscopy structures of the activated GPR55 in complex with heterotrimeric G and two structurally diverse ligands: the putative endogenous agonist 1-palmitoyl-2-lysophosphatidylinositol (LPI) and the synthetic agonist ML184. These results reveal insights into ligand recognition at GPR55, G protein coupling and receptor activation. Notably, an orthosteric binding site opening towards the membrane is observed in both structures, enabling direct interaction of the agonists with membrane lipids. The structural observations are supported by mutagenesis and functional experiments employing G protein dissociation assays. These findings will be of importance for the structure-based development of drugs targeting GPR55.

PubMed: 40000629
DOI: 10.1038/s41467-025-57204-y

実験手法

ELECTRON MICROSCOPY (2.51 Å)