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- EMDB-61836: Cryo-EM structure of transporter2a1_PGE2 -

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Basic information

Entry
Database: EMDB / ID: EMD-61836
TitleCryo-EM structure of transporter2a1_PGE2
Map data
Sample
  • Complex: complex of transporter2a1_pge2
    • Protein or peptide: Solute carrier organic anion transporter family member 2A1
  • Ligand: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid
KeywordsMFS transporter / TRANSPORT PROTEIN
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
Solute carrier organic anion transporter family member 2A1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsJiang DH / Xia ZY
Funding support China, 1 items
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, 2024-
Header (metadata) releaseSep 10, 2025-
Map releaseSep 10, 2025-
UpdateSep 10, 2025-
Current statusSep 10, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_61836.png

Downloads & links

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Map

FileDownload / File: emd_61836.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 320 pix.
= 272. Å		0.85 Å/pix.
x 320 pix.
= 272. Å		0.85 Å/pix.
x 320 pix.
= 272. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.562
Minimum - Maximum-2.27582 - 3.7790184
Average (Standard dev.)-0.0029474115 (±0.071125746)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 272.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_61836_half_map_1.map
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_61836_half_map_2.map
Projections & Slices
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Sample components

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Entire : complex of transporter2a1_pge2

EntireName: complex of transporter2a1_pge2
Components
  • Complex: complex of transporter2a1_pge2
    • Protein or peptide: Solute carrier organic anion transporter family member 2A1
  • Ligand: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid

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Supramolecule #1: complex of transporter2a1_pge2

SupramoleculeName: complex of transporter2a1_pge2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Solute carrier organic anion transporter family member 2A1

MacromoleculeName: Solute carrier organic anion transporter family member 2A1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 70.103898 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGLLPKLGAS QGSDTSTSRA GRCARSVFGN IKVFVLCQGL LQLCQLLYSA YFKSSLTTIE KRFGLSSSSS GLISSLNEIS NAILIIFVS YFGSRVHRPR LIGIGGLFLA AGAFILTLPH FLSEPYQYTL ASTGNNSRLQ AELCQKHWQD LPPSKCHSTT Q NPQKETSS ...String:
MGLLPKLGAS QGSDTSTSRA GRCARSVFGN IKVFVLCQGL LQLCQLLYSA YFKSSLTTIE KRFGLSSSSS GLISSLNEIS NAILIIFVS YFGSRVHRPR LIGIGGLFLA AGAFILTLPH FLSEPYQYTL ASTGNNSRLQ AELCQKHWQD LPPSKCHSTT Q NPQKETSS MWGLMVVAQL LAGIGTVPIQ PFGISYVDDF SEPSNSPLYI SILFAISVFG PAFGYLLGSV MLQIFVDYGR VN TAAVNLV PGDPRWIGAW WLGLLISSAL LVLTSFPFFF FPRAMPIGAK RAPATADEAR KLEEAKSRGS LVDFIKRFPC IFL RLLMNS LFVLVVLAQC TFSSVIAGLS TFLNKFLEKQ YGTSAAYANF LIGAVNLPAA ALGMLFGGIL MKRFVFSLQA IPRI ATTII TISMILCVPL FFMGCSTPTV AEVYPPSTSS SIHPQSPACR RDCSCPDSIF HPVCGDNGIE YLSPCHAGCS NINMS SATS KQLIYLNCSC VTGGSASAKT GSCPVPCAHF LLPAIFLISF VSLIACISHN PLYMMVLRVV NQEEKSFAIG VQFLLM RLL AWLPSPALYG LTIDHSCIRW NSLCLGRRGA CAYYDNDALR DRYLGLQMGY KALGMLLLCF ISWRVKKNKE YNVQKAA GL I

UniProtKB: Solute carrier organic anion transporter family member 2A1

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Macromolecule #2: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-...

MacromoleculeName: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid
type: ligand / ID: 2 / Number of copies: 1 / Formula: P2E
Molecular weightTheoretical: 352.465 Da
Chemical component information

ChemComp-P2E:
(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 259151
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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