9WIJSummary for 9WIJ
| Entry DOI | 10.2210/pdb9wij/pdb |
| EMDB information | 65995 |
| Descriptor | G-protein coupled receptor 84,Soluble cytochrome b562, 9-(2-cyclopropylethynyl)-2-[[(2~{S})-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one (2 entities in total) |
| Functional Keywords | gpcr, signaling protein, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 50615.99 |
| Authors | Suzuki, S.,Nishikawa, K.,Tran, D.P.,Akio, K.,Fujiyoshi, Y. (deposition date: 2025-08-28, release date: 2026-07-01, Last modification date: 2026-07-29) |
| Primary citation | Suzuki, S.,Tran, D.P.,Nishikawa, K.,Kitao, A.,Fujiyoshi, Y. Mechanistic insight into signal bias by the agonist-dependent conformational dynamics of GPR84. Nat Commun, 2026 Cited by PubMed Abstract: GPR84 is an orphan class A GPCR primarily expressed in immune cells, where it plays key roles in inflammation and metabolism. Here, we present the cryo-electron microscopy structures of the GPR84-Gi complex bound to the G protein-biased agonist DL-175, and the inactive state of GPR84 bound to the antagonist GLPG1205. Combined with signaling assays and molecular dynamics simulations, these structures elucidate the conformational landscape spanning the inactive and G protein-biased active states of GPR84, providing a mechanistic basis for biased agonism. Notably, steric interactions between DL-175 and L336 selectively preclude the conformational changes required for efficient β-arrestin recruitment without compromising G protein activation. These structural insights provide a structural context for the rational design of GPR84-targeted therapeutics with precisely tuned signaling profiles. PubMed: 42463693DOI: 10.1038/s41467-026-75728-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.05 Å) |
Structure validation
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