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Yorodumi- EMDB-71657: Cryo-EM structure ONO3030297-bound prostaglandin D2 receptor (DP1... -
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Basic information
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| Title | Cryo-EM structure ONO3030297-bound prostaglandin D2 receptor (DP1)-bRIL-Fab complex (Fab-focused map) | |||||||||
Map data | structure ONO3030297-bound prostaglandin D2 receptor (DP1)-bRIL-Fab complex (Fab-focused map) | |||||||||
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Keywords | GPCR / cryo-EM / DP1 / inverse agonist / ONO3030297 / prostaglandin D2 receptor / prostanoid DP receptor / PGD receptor / PTGDR / DP1-bRIL chimera / MEMBRANE PROTEIN | |||||||||
| Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.67 Å | |||||||||
Authors | Davoudinasab B / Kim D / Cherezov V / Han GW | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2025Title: Structural insights into the mechanism of activation and inhibition of the prostaglandin D2 receptor 1. Authors: Behnaz Davoudinasab / Aleksey Raskovalov / Woojin Lee / Donggyun Kim / Heesoo Kim / Jordy Homing Lam / Gye Won Han / Vsevolod Katritch / Vadim Cherezov / ![]() 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 ...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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_71657.map.gz | 108.6 MB | EMDB map data format | |
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| Header (meta data) | emd-71657-v30.xml emd-71657.xml | 16.9 KB 16.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_71657_fsc.xml | 12.6 KB | Display | FSC data file |
| Images | emd_71657.png | 42 KB | ||
| Masks | emd_71657_msk_1.map | 216 MB | Mask map | |
| Filedesc metadata | emd-71657.cif.gz | 5.2 KB | ||
| Others | emd_71657_half_map_1.map.gz emd_71657_half_map_2.map.gz | 200.3 MB 200.3 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-71657 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-71657 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_71657.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | structure ONO3030297-bound prostaglandin D2 receptor (DP1)-bRIL-Fab complex (Fab-focused map) | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_71657_msk_1.map | ||||||||||||
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| Density Histograms |
-Half map: Half Map A
| File | emd_71657_half_map_1.map | ||||||||||||
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| Annotation | Half Map A | ||||||||||||
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| Density Histograms |
-Half map: Half Map B
| File | emd_71657_half_map_2.map | ||||||||||||
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| Annotation | Half Map B | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : ONO3030297 bound to DP1 bRIL-BAG2Fab-Nb complex
| Entire | Name: ONO3030297 bound to DP1 bRIL-BAG2Fab-Nb complex |
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| Components |
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-Supramolecule #1: ONO3030297 bound to DP1 bRIL-BAG2Fab-Nb complex
| Supramolecule | Name: ONO3030297 bound to DP1 bRIL-BAG2Fab-Nb complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: anti-BRIL Fab Heavy Chain
| Macromolecule | Name: anti-BRIL Fab Heavy Chain / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: synthetic construct (others) |
| Recombinant expression | Organism: ![]() |
| Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVVDFSLHWV RQAPGKGLEW VAYISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARWGYWPGEP WWKAFDYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY F PEPVTVSW ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVVDFSLHWV RQAPGKGLEW VAYISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARWGYWPGEP WWKAFDYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY F PEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKKVEPK S |
-Macromolecule #2: anti-BRIL Fab Light Chain
| Macromolecule | Name: anti-BRIL Fab Light Chain / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: synthetic construct (others) |
| Recombinant expression | Organism: ![]() |
| Sequence | String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYLYYSLVT FGQGTKVEIK RTVAAPSVFI FPPSDSQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYLYYSLVT FGQGTKVEIK RTVAAPSVFI FPPSDSQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRG |
-Macromolecule #3: anti-Fab Nanobody
| Macromolecule | Name: anti-Fab Nanobody / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: synthetic construct (others) |
| Recombinant expression | Organism: ![]() |
| Sequence | String: GSQVQLQESG GGLVQPGGSL RLSCAASGRT ISRYAMSWFR QAPGKEREFV AVARRSGDGA FYADSVQGRF TVSRDDAKNT VYLQMNSLK PEDTAVYYCA IDSDTFYSGS YDYWGQGTQV TVSS |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 65.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation










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Processing
FIELD EMISSION GUN


