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- EMDB-58351: UapA (WT) in DDM, Apo state -

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Basic information

Entry
Database: EMDB / ID: EMD-58351
TitleUapA (WT) in DDM, Apo state
Map dataUnsharpened map. Very clean but lacks ultra high resolution features
Sample
  • Complex: UapA (WT) in DDM, Apo state
    • Protein or peptide: Uric acid-xanthine permease
  • Ligand: DODECYL-BETA-D-MALTOSIDE
  • Ligand: MYRISTIC ACID
  • Ligand: PALMITIC ACID
  • Ligand: ERGOSTEROL
  • Ligand: LAURIC ACID
  • Ligand: DIACYL GLYCEROL
  • Ligand: water
KeywordsUapA / DDM / Transporter / Inward-facing / Uric Acid / Xanthine / MEMBRANE PROTEIN
Function / homology
Function and homology information


xanthine transport / xanthine transmembrane transporter activity / autophagosome lumen / purine nucleobase binding / urate transport / urate transmembrane transporter activity / fungal-type vacuole / endosome membrane / plasma membrane
Similarity search - Function
Xanthine/uracil permease / Xanthine/uracil permeases family signature. / Nucleobase cation symporter 2 family / Permease family
Similarity search - Domain/homology
Uric acid-xanthine permease
Similarity search - Component
Biological speciesAspergillus nidulans FGSC A4 (mold)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.06 Å
AuthorsBroutzakis G / Gatsogiannis C
Funding support Germany, 2 items
OrganizationGrant numberCountry
German Research Foundation (DFG)496113311 Germany
German Research Foundation (DFG)211/667-1 Germany
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: Cryo-EM of the eukaryotic purine transporter UapA demonstrates intramolecular and lipid regulation of transport.
Authors: George Broutzakis / Yiannis Pyrris / Ifigeneia Akrani / Alexander Neuhaus / Emmanuel Mikros / George Diallinas / Christos Gatsogiannis /
Abstract: Members of the nucleobase ascorbate transporter (NAT) family (SLC23) are elevator-type transporters that are responsible for the uptake of nucleobases and ascorbate. In fungi, NAT members are also ...Members of the nucleobase ascorbate transporter (NAT) family (SLC23) are elevator-type transporters that are responsible for the uptake of nucleobases and ascorbate. In fungi, NAT members are also responsible for the specific uptake of antifungal nucleobase analogues, such as oxypurinol, allopurinol, or 8-azaguanine. Here, we report nearly full-length cryo-EM structures of UapA, a high-affinity purine transporter from the model fungus , in inward-facing apo- and substrate-loaded conformations at 2.06 to 3.5 Å in detergent and lipid nanodiscs. The high-resolution structures reveal the role of water molecules and lipids in substrate binding, specificity, transporter dimerization, and activity. Notably, the N-tail of UapA is found to be structured, interacting with both the core and scaffold domains, which in combination with functional data suggests a dual role in trafficking and transport dynamics. Overall, our study provides unprecedented structural and functional insights into an elevator-type fungal transporter, which may well contribute to the exploitation of NAT transporters as specific gateways for targeted pharmacological antifungal approaches.
History
DepositionJun 1, 2026-
Header (metadata) releaseJul 1, 2026-
Map releaseJul 1, 2026-
UpdateJul 8, 2026-
Current statusJul 8, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_58351.png

Downloads & links

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Map

FileDownload / File: emd_58351.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationUnsharpened map. Very clean but lacks ultra high resolution features
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.74 Å/pix.
x 350 pix.
= 257.6 Å		0.74 Å/pix.
x 350 pix.
= 257.6 Å		0.74 Å/pix.
x 350 pix.
= 257.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.736 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.069
Minimum - Maximum-0.14307255 - 0.31970987
Average (Standard dev.)0.00057194574 (±0.0073313247)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions350350350
Spacing350350350
CellA=B=C: 257.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_58351_msk_1.map
Projections & Slices
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Additional map: Model-free density modified map

Fileemd_58351_additional_1.map
AnnotationModel-free density modified map
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Additional map: Sharpened map

Fileemd_58351_additional_2.map
AnnotationSharpened map
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: Half map B

Fileemd_58351_half_map_1.map
AnnotationHalf map B
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Half map: Half map A

Fileemd_58351_half_map_2.map
AnnotationHalf map A
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Sample components

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Entire : UapA (WT) in DDM, Apo state

EntireName: UapA (WT) in DDM, Apo state
Components
  • Complex: UapA (WT) in DDM, Apo state
    • Protein or peptide: Uric acid-xanthine permease
  • Ligand: DODECYL-BETA-D-MALTOSIDE
  • Ligand: MYRISTIC ACID
  • Ligand: PALMITIC ACID
  • Ligand: ERGOSTEROL
  • Ligand: LAURIC ACID
  • Ligand: DIACYL GLYCEROL
  • Ligand: water

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Supramolecule #1: UapA (WT) in DDM, Apo state

SupramoleculeName: UapA (WT) in DDM, Apo state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Aspergillus nidulans FGSC A4 (mold) / Strain: A4
Molecular weightTheoretical: 120 KDa

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Macromolecule #1: Uric acid-xanthine permease

MacromoleculeName: Uric acid-xanthine permease / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Aspergillus nidulans FGSC A4 (mold)
Molecular weightTheoretical: 60.291586 KDa
Recombinant expressionOrganism: Saccharomyces cerevisiae (brewer's yeast)
SequenceString: MGPDSVIPNS NPKKTVRQRV RLLARHLTTR EGLIGDYDYG FLFRPELPFM KKDPRAPPFF GLNEKIPVLL AFILGLQHAL AMLAGVVTP PLIISSSLSL PSDLQQYLVS TSLIVCGLLS MVQITRFHIY KTPYYIGSGV LSVMGVSFSI ISVASGAFNQ M YSNGFCQL ...String:
MGPDSVIPNS NPKKTVRQRV RLLARHLTTR EGLIGDYDYG FLFRPELPFM KKDPRAPPFF GLNEKIPVLL AFILGLQHAL AMLAGVVTP PLIISSSLSL PSDLQQYLVS TSLIVCGLLS MVQITRFHIY KTPYYIGSGV LSVMGVSFSI ISVASGAFNQ M YSNGFCQL DEAGNRLPCP EAYGALIGTS ACCALVEILL AFVPPKVIQK IFPPIVTGPT VMLIGISLIG TGFKDWAGGS AC MDDGMLC PSATAPRPLP WGSPEFIGLG FLVFVSIILC ERFGAPIMKS CSVVIGLLVG CIVAAACGYF SHADIDAAPA ASF IWVKTF PLSVYGPMVL PIIAVFIICA CECIGDVTAT CDVSRLEVRG GTFESRIQGA VLADGINSVV AALATMTPMT TFAQ NNGVI ALTRCANRWA GYCCCLILIV AGIFAKFAAA IVAIPNSVMG GMKTFLFASV VISGQAIVAK APFTRRNRFI LTASM ALGY GATLVPTWFG NVFPQTENRD LEGFENAIEL VLETGFAVTA FVAMLLNAIM PAEVEEIGAV TPMPVSAHDN RDGEAE YQS KQA

UniProtKB: Uric acid-xanthine permease

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Macromolecule #2: DODECYL-BETA-D-MALTOSIDE

MacromoleculeName: DODECYL-BETA-D-MALTOSIDE / type: ligand / ID: 2 / Number of copies: 14 / Formula: LMT
Molecular weightTheoretical: 510.615 Da
Chemical component information

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

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Macromolecule #3: MYRISTIC ACID

MacromoleculeName: MYRISTIC ACID / type: ligand / ID: 3 / Number of copies: 22 / Formula: MYR
Molecular weightTheoretical: 228.371 Da
Chemical component information

ChemComp-MYR:
MYRISTIC ACID

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Macromolecule #4: PALMITIC ACID

MacromoleculeName: PALMITIC ACID / type: ligand / ID: 4 / Number of copies: 6 / Formula: PLM
Molecular weightTheoretical: 256.424 Da
Chemical component information

ChemComp-PLM:
PALMITIC ACID

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Macromolecule #5: ERGOSTEROL

MacromoleculeName: ERGOSTEROL / type: ligand / ID: 5 / Number of copies: 8 / Formula: ERG
Molecular weightTheoretical: 396.648 Da
Chemical component information

ChemComp-ERG:
ERGOSTEROL

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Macromolecule #6: LAURIC ACID

MacromoleculeName: LAURIC ACID / type: ligand / ID: 6 / Number of copies: 14 / Formula: DAO
Molecular weightTheoretical: 200.318 Da
Chemical component information

ChemComp-DAO:
LAURIC ACID

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Macromolecule #7: DIACYL GLYCEROL

MacromoleculeName: DIACYL GLYCEROL / type: ligand / ID: 7 / Number of copies: 4 / Formula: DGA
Molecular weightTheoretical: 625.018 Da
Chemical component information

ChemComp-DGA:
DIACYL GLYCEROL

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Macromolecule #8: water

MacromoleculeName: water / type: ligand / ID: 8 / Number of copies: 404 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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

Concentration5 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
20.0 mMC4H11NO3Tris
150.0 mMNaClSodium Chloride
0.03 %C24H46O11DDM
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 286.15 K / Instrument: FEI VITROBOT MARK IV
Details: Vitrification chamber was allowed to equilibrate for 15 min at 100% humidity..

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 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: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.06 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.5.1) / Number images used: 499617
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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