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Open data
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Basic information
Entry | Database: PDB / ID: 9uwd | |||||||||||||||||||||
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Title | Cryo-EM structure of inactive-DP1 | |||||||||||||||||||||
![]() | Prostaglandin D2 receptor,Soluble cytochrome b562 | |||||||||||||||||||||
![]() | MEMBRANE PROTEIN / GPCR / DP1 / inactive | |||||||||||||||||||||
Function / homology | ![]() prostaglandin J receptor activity / prostaglandin D receptor activity / Prostanoid ligand receptors / adenosine metabolic process / cellular response to prostaglandin D stimulus / male sex determination / sleep / mast cell degranulation / electron transport chain / positive regulation of cytosolic calcium ion concentration ...prostaglandin J receptor activity / prostaglandin D receptor activity / Prostanoid ligand receptors / adenosine metabolic process / cellular response to prostaglandin D stimulus / male sex determination / sleep / mast cell degranulation / electron transport chain / positive regulation of cytosolic calcium ion concentration / G alpha (s) signalling events / periplasmic space / electron transfer activity / G protein-coupled receptor signaling pathway / inflammatory response / iron ion binding / heme binding / membrane / plasma membrane Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.41 Å | |||||||||||||||||||||
![]() | Xu, J. / Xu, Y. / Wu, C. / Xu, H.E. | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis for ligand recognition and receptor activation of the prostaglandin D2 receptor DP1. Authors: Jiuyin Xu / Yanli Wu / Youwei Xu / Yang Li / Xinheng He / Heng Zhang / James Jiqi Wang / Jingjing Hou / Junrui Li / Wen Hu / Kai Wu / Qingning Yuan / Canrong Wu / H Eric Xu / ![]() Abstract: The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates critical physiological and pathological processes, ranging from sleep regulation to inflammatory responses and ...The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates critical physiological and pathological processes, ranging from sleep regulation to inflammatory responses and cardiovascular function. Despite its therapeutic significance, structural insights into DP1 activation mechanisms have remained elusive. Here, using cryoelectron microscopy (cryo-EM), we determined high-resolution structures of human DP1 in both inactive and active states, with the latter captured in complex with its endogenous agonist PGD2 or the synthetic agonist BW245C, bound to the stimulatory G protein, Gs. Our structures, coupled with functional and mutagenesis studies, unveiled unique structural features of DP1, including an alternative activation mechanism, ligand-selectivity determinants, and G protein coupling characteristics. These molecular insights provide a rational framework for designing selective DP1-targeted therapeutics, both agonists and antagonists, with enhanced specificity and reduced off-target effects, opening broad avenues for treating DP1-associated disorders. | |||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 92.2 KB | Display | ![]() |
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PDB format | ![]() | 69.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 27.4 KB | Display | |
Data in CIF | ![]() | 36 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 64550MC ![]() 8zvzC ![]() 8zw0C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 47773.949 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: PTGDR, cybC / Production host: ![]() |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: DP1 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 41270 / Symmetry type: POINT |