9GE3
Structure of GPR55 in complex with G13 and endogenous lipid agonist lysophosphatidylinositol
This is a non-PDB format compatible entry.
Summary for 9GE3
| Entry DOI | 10.2210/pdb9ge3/pdb |
| EMDB information | 51288 |
| Descriptor | 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, ... (8 entities in total) |
| Functional Keywords | g protein-coupled receptor, gpcr, lipid agonist, cholesterol, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 175486.12 |
| Authors | |
| Primary citation | 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 Cited by 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: 40000629DOI: 10.1038/s41467-025-57204-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.87 Å) |
Structure validation
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