9V6T
Cryo-EM structure of the GLPG1205-bound GPR84 receptor
This is a non-PDB format compatible entry.
Summary for 9V6T
| Entry DOI | 10.2210/pdb9v6t/pdb |
| Related | 9UPY |
| EMDB information | 64407 64807 |
| Descriptor | Soluble cytochrome b562, anti-BRIL Fab Heavy chain, anti-BRIL Fab Light chain, ... (5 entities in total) |
| Functional Keywords | gpcr, mcfa, complex, antagonist, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 82811.49 |
| Authors | |
| Primary citation | Choi, M.K.,Park, D.J.,Kim, P.,Choi, H.S.,Myung, S.,Yoo, Y.,Chang, N.,Yoon, G.Y.,Kang, H.J.,Ha, S.J.,Cho, H.S. Pharmacological modulation of GPR84 revealed by dual states structures and immune functional assays. Exp.Mol.Med., 2026 Cited by PubMed Abstract: G-protein-coupled receptor 84 (GPR84) is an orphan class A GPCR selectively activated by medium chain fatty acids and highly expressed in immune cells, where it modulates pro-inflammatory signaling. The structural basis of GPR84 inactivation and antagonism has remained unclear, limiting the rational design of pathway-selective modulators despite its clinical relevance in metabolic inflammation and fibrotic diseases. Here, we report cryo-electron microscopy structures of human GPR84 in inactive and active states. The 3.5 Å inactive structure bound to the antagonist GLPG1205 reveals a lid-like conformation of extracellular loop 2 and an inward reorientation of Arg172, with the antagonist head group blocking the allosteric sodium-binding site. Molecular dynamics simulations further support these findings, identifying an aberrant TM5, TM6 lateral entry gate. By contrast, the 3.17 Å agonist ZQ-16, Gαi complex, shows a rearranged toggle switch and comparative analyses highlight extracellular loop 2 conformational plasticity. Immune functional assays in THP-1 cells demonstrated that ZQ-16 elicited GPR84-dependent activation and cytokine production, which were effectively abrogated by GLPG1205. Mutagenesis combined with functional assays validates key ligand interactions, providing a framework for the rational design of pathway selective GPR84 modulators. PubMed: 42722702DOI: 10.1038/s12276-026-01841-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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