9EI5
Cryo-EM structure of Apo form of prostaglandin D2 receptor (DP1)-bRIL-Fab complex
Summary for 9EI5
| Entry DOI | 10.2210/pdb9ei5/pdb |
| EMDB information | 48077 |
| Descriptor | Prostaglandin D2 receptor,Soluble cytochrome b562, anti-BRIL Fab Heavy Chain, anti-Fab Nanobody synthetic construct, ... (4 entities in total) |
| Functional Keywords | gpcr, cryo-em, dp1, apo form, prostaglandin d2 receptor, prostanoid dp receptor, pgd receptor, ptgdr, dp1-bril chimera, membrane protein, membrane protein-immune system complex, membrane protein/immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 116753.58 |
| Authors | Davoudinasab, B.,Cherezov, V.,Han, G.W. (deposition date: 2024-11-25, release date: 2025-09-03, Last modification date: 2025-10-22) |
| Primary citation | Davoudinasab, B.,Raskovalov, A.,Lee, W.,Kim, D.,Kim, H.,Lam, J.H.,Han, G.W.,Katritch, V.,Cherezov, V. Structural insights into the mechanism of activation and inhibition of the prostaglandin D2 receptor 1. Nat Commun, 16:8944-8944, 2025 Cited by PubMed Abstract: The prostaglandin D2 receptor 1 (DP1), a member of the prostanoid G protein-coupled receptor (GPCR) family, plays critical roles in allergic responses, sleep regulation, immune modulation, and vasodilation. Here, we present five high-resolution cryo-electron microscopy (cryo-EM) structures of the human DP1 receptor, including an apo structure, two inactive state structures bound to two different inverse agonists developed by ONO Pharmaceutical, and two active state structures in complex with the G protein and bound to the endogenous agonist PGD2 and its selective derivative BW245C. Structural analysis, complemented by molecular dynamics simulations and site-directed mutagenesis, reveals key residues involved in ligand recognition and suggests a distinct activation mechanism for DP1, which lacks most of the conserved class A GPCR motifs. Notably, the unique residue K76 within the conserved sodium pocket acts as a major activation switch, while amphiphilic helix 8 adopts an unconventional orientation essential for receptor function. These findings offer valuable insights into the structure and function of prostanoid receptors and may facilitate the development of therapeutics targeting DP1. PubMed: 41062467DOI: 10.1038/s41467-025-64002-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.84 Å) |
Structure validation
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