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- PDB-9mgk: Human prostaglandin transporter(OATP2A1) -

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Basic information

Entry
Database: PDB / ID: 9mgk
TitleHuman prostaglandin transporter(OATP2A1)
ComponentsSolute carrier organic anion transporter family member 2A1
KeywordsTRANSPORT PROTEIN / Prostaglandin / OATP / transporter / MEMBRANE PROTEIN
Function / homology
Function and homology information


Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2) / Transport of organic anions / sodium-independent organic anion transport / sodium-independent organic anion transmembrane transporter activity / prostaglandin transport / prostaglandin transmembrane transporter activity / lipid transporter activity / lipid transport / basal plasma membrane / basolateral plasma membrane ...Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2) / Transport of organic anions / sodium-independent organic anion transport / sodium-independent organic anion transmembrane transporter activity / prostaglandin transport / prostaglandin transmembrane transporter activity / lipid transporter activity / lipid transport / basal plasma membrane / basolateral plasma membrane / lysosome / membrane / plasma membrane
Similarity search - Function
Organic anion transporter polypeptide / Organic Anion Transporter Polypeptide (OATP) family / Kazal-type serine protease inhibitor domain / Kazal domain superfamily / Kazal domain / Kazal domain profile. / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier organic anion transporter family member 2A1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å
AuthorsYu, P. / Orlando, M.A. / Orlando, B.J.
Funding support United States, 1items
OrganizationGrant numberCountry
Not funded United States
CitationJournal: Commun Biol / Year: 2025
Title: Structure and post-translational modification of the prostaglandin transporter.
Authors: Peixuan Yu / Melanie A Orlando / Benjamin J Orlando /
Abstract: The prostaglandin transporter (PGT) is a member of the OATP family of membrane transporters. PGT mediates the uptake of prostaglandins from the extracellular environment to enable intracellular ...The prostaglandin transporter (PGT) is a member of the OATP family of membrane transporters. PGT mediates the uptake of prostaglandins from the extracellular environment to enable intracellular enzymatic degradation and termination of signaling. In addition to importing prostaglandins, PGT is also an essential core component of the Maxi-Cl channel, which facilitates cellular release of ATP and other small organic anions. Despite progress on understanding the (patho)physiological roles of PGT, and development of small molecules to inhibit this transporter, molecular details of the overall structure and transport mechanism remain elusive. Here we determined the cryo-EM structure of human PGT, which demonstrates an overall topology consistent with other OATPs despite possessing a dual transporter/channel functionality. We additionally investigated the role of eight potential disulfide bonds found in the extracellular loops of PGT and paralogous transporters. We demonstrate that six intra-loop disulfide bonds (C420-C511, C450-C470, C492-C474, C459-C507, C444-C494, C580-C594) are essential for proper N-glycosylation, plasma membrane trafficking, and prostaglandin import activity. In contrast, two inter-loop disulfides (C155-C587 and C143-C448) restricted maximal prostaglandin uptake, suggesting a possible regulatory role in modulating PGT activity. In total, our studies provide a fresh molecular perspective on the structure, post-translational modification, and overall function of PGT.
History
DepositionDec 11, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 23, 2025Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
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Revision 1.0Jul 23, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
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Revision 1.1Jul 30, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Solute carrier organic anion transporter family member 2A1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,0223
Polymers74,5641
Non-polymers2,4592
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Solute carrier organic anion transporter family member 2A1 / SLCO2A1 / OATP2A1 / PHOAR2 / Prostaglandin transporter / PGT / Solute carrier family 21 member 2 / SLC21A2


Mass: 74563.570 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Twin strep tag and a TEV cleavage site at the N terminus of PGT.
Source: (gene. exp.) Homo sapiens (human) / Gene: SLCO2A1, OATP2A1, SLC21A2 / Plasmid: pcDNA3.0 / Cell (production host): HEK293F / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q92959
#2: Chemical ChemComp-AJP / Digitonin


Mass: 1229.312 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C56H92O29 / Comment: detergent*YM
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: human prostaglandin transporter OATP2A1 / Type: COMPLEX
Details: purified detergent solubilized prostaglandin transporter
Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.0745 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human) / Cellular location: plasma membrane
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293F / Plasmid: pCDNA3.0
Buffer solutionpH: 8 / Details: 25mM HEPES pH8.0, 150mM NaCl,0.06% digitonin
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMSodium ChlorideNaCl1
225 mM4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid1
30.06 w/vdigitoninC56H92O291
SpecimenConc.: 3.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: Glow discharge in a Pelco EasyGlow 45s at 15mA. / Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: ZEMLIN TABLEAU
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 44.48 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9088

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Processing

EM software
IDNameVersionCategoryDetails
1cryoSPARC4.4.1particle selection
4cryoSPARC4.4.1CTF correctionPatch CTF estimation
7UCSF Chimera1.16model fitting
9cryoSPARC4.4.1initial Euler assignment
10RELION5final Euler assignment
11RELION5classification
12RELION53D reconstruction
13PHENIX1.21.1_5286model refinement
Image processingDetails: The images were corrected for beam induced motion using patch motion correction in cryoSPARC.
CTF correctionDetails: Patch CTF estimation was performed in cryoSPARC. / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1795004
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45842 / Algorithm: BACK PROJECTION / Num. of class averages: 1 / Symmetry type: POINT
Atomic model buildingProtocol: OTHER / Space: REAL / Details: Refinement in phenix.real_space_refine
Atomic model buildingChain residue range: 1-643 / Source name: AlphaFold / Type: in silico model
RefinementHighest resolution: 4.3 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0034248
ELECTRON MICROSCOPYf_angle_d0.6935798
ELECTRON MICROSCOPYf_dihedral_angle_d5.838801
ELECTRON MICROSCOPYf_chiral_restr0.046697
ELECTRON MICROSCOPYf_plane_restr0.005696

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