21TY
Cryo-EM structure of Free fatty acid receptor 2 (FFA2)-ARK1 with GLPG0974
This is a non-PDB format compatible entry.
Summary for 21TY
| Entry DOI | 10.2210/pdb21ty/pdb |
| EMDB information | 67995 |
| Descriptor | Free fatty acid receptor 2,human free fatty acid receptor 2 (FFA2) fused with de novo designed ARK1, GLPG-0974 (3 entities in total) |
| Functional Keywords | gpcr, ffa2, free fatty acid receptor 2, glpg0974, ark1, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 86050.45 |
| Authors | Kojima, A.,Kawakami, K.,Narita, T.,Kugawa, M.,Hayashi, K.,Fukuda, M.,Kato, H.E. (deposition date: 2025-12-26, release date: 2026-09-09) |
| Primary citation | Kojima, A.,Kawakami, K.,Kobayashi, N.,Kobayashi, K.,Matsui, T.E.,Uemoto, K.,Gu, Y.,Narita, T.J.,Kugawa, M.,Fukuda, M.,Kato, H.E. Universal pipeline for high-resolution GPCR structure determination. Nat.Struct.Mol.Biol., 2026 Cited by PubMed Abstract: G protein-coupled receptors (GPCRs) regulate human physiology and are major drug targets. Although cryo-electron microscopy has accelerated GPCR structural biology, inactive-state structures remain difficult because current fusion-based strategies often require extensive experimental screening to identify rigid constructs suitable for high-resolution reconstruction. Here we introduce a universal pipeline that integrates an in silico fusion construct screening program, NOAH (nonexperimental, artificial-intelligence-assisted, high-throughput construct screening for structural analysis), with a de novo designed fusion protein, ARK1 (artificially designed fiducial marker). NOAH enabled structure determination of vasopressin V2 receptor bound to the antagonist tolvaptan or partial agonist OPC51803 and bradykinin B2 receptor bound to the antagonist icatibant, revealing receptor activation and inhibition mechanisms. Coupling NOAH to ARK1 improved the V2 receptor-tolvaptan map and enabled high-resolution structures of lysophosphatidic acid receptor 2 bound to Ki16425 and free fatty acid receptor 2 bound to GLPG0974. NOAH-ARK1 minimizes trial-and-error construct optimization and provides a broadly applicable route for GPCR structural analysis and drug discovery. PubMed: 42665663DOI: 10.1038/s41594-026-01869-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.93 Å) |
Structure validation
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