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- PDB-9jv1: Cryo-EM structure of transporter2a1_PGE2 -

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Basic information

Entry
Database: PDB / ID: 9jv1
TitleCryo-EM structure of transporter2a1_PGE2
ComponentsSolute carrier organic anion transporter family member 2A1
KeywordsTRANSPORT PROTEIN / MFS transporter
Function / homology
Function and homology information


Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2) / Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / 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) / Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / 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
Chem-P2E / Solute carrier organic anion transporter family member 2A1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsJiang, D.H. / Xia, Z.Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31971134 China
CitationJournal: Nat Commun / Year: 2025
Title: Structure and transport mechanism of the human prostaglandin transporter SLCO2A1.
Authors: Zhanyi Xia / Guangyuan Lu / Di Wu / Jun Zhao / Bowen Zhang / Haoran Xu / Yingying Du / Daohua Jiang /
Abstract: SLCO2A1 is a member of the organic anion transporting polypeptide (OATP) family, which preferentially transports prostaglandins (PGs) into cells and plays a vital role in regulating PGs inactivation ...SLCO2A1 is a member of the organic anion transporting polypeptide (OATP) family, which preferentially transports prostaglandins (PGs) into cells and plays a vital role in regulating PGs inactivation and distribution. Dysregulation or genetic mutation of SLCO2A1 is associated with primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with the SLCO2A1 gene (CEAS). Although the biophysical and biochemical properties of SLCO2A1 have been characterized, the precise mechanism by which SLCO2A1 recognizes and transports PGs remains unclear. Here, we present the cryo-electron microscopy structures of human SLCO2A1 in apo and PGE-bound forms, revealing the detailed structural features and structural basis for PGs transport. Fatty acid-like PGE binds in the central cavity, engaging in specific interactions with W565 and two serine residues, which are not conserved in other OATPs. Combined with functional assays and structural comparisons, this study offers mechanistic insights into PGE recognition, substrate selectivity, conformational changes, and pathology of SLCO2A1.
History
DepositionOct 8, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Sep 10, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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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)70,4562
Polymers70,1041
Non-polymers3521
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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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: 70103.898 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLCO2A1, OATP2A1, SLC21A2 / Production host: Homo sapiens (human) / References: UniProt: Q92959
#2: Chemical ChemComp-P2E / (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / Prostaglandin E2


Mass: 352.465 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H32O5 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
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: complex of transporter2a1_pge2 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 259151 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0044168
ELECTRON MICROSCOPYf_angle_d0.5415664
ELECTRON MICROSCOPYf_dihedral_angle_d7.432572
ELECTRON MICROSCOPYf_chiral_restr0.042659
ELECTRON MICROSCOPYf_plane_restr0.004700

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