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- EMDB-53508: Cryo-EM structure of human MATE1 -

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Basic information

Entry
Database: EMDB / ID: EMD-53508
TitleCryo-EM structure of human MATE1
Map data
Sample
  • Complex: Human multidrug and toxin extrusion protein (MATE1) in complex with Fab
    • Protein or peptide: Multidrug and toxin extrusion protein 1
    • Protein or peptide: Heavy chain of Fab
    • Protein or peptide: Light chain of Fab
  • Ligand: CHOLESTEROL
  • Ligand: water
KeywordsSLC47A1 / apo / Fab / multidrug transporter / TRANSPORT PROTEIN
Function / homology
Function and homology information


L-arginine import across plasma membrane / polyspecific organic cation:proton antiporter activity / L-alpha-amino acid transmembrane transport / putrescine transmembrane transporter activity / L-arginine transmembrane transporter activity / organic cation transport / : / : / putrescine transport / thiamine transmembrane transporter activity ...L-arginine import across plasma membrane / polyspecific organic cation:proton antiporter activity / L-alpha-amino acid transmembrane transport / putrescine transmembrane transporter activity / L-arginine transmembrane transporter activity / organic cation transport / : / : / putrescine transport / thiamine transmembrane transporter activity / L-amino acid transmembrane transporter activity / amino acid import across plasma membrane / xenobiotic transmembrane transport / xenobiotic detoxification by transmembrane export across the plasma membrane / antiporter activity / xenobiotic transport / transmembrane transporter activity / xenobiotic transmembrane transporter activity / transmembrane transport / basolateral plasma membrane / apical plasma membrane / membrane / plasma membrane
Similarity search - Function
Multidrug and toxic compound extrusion family, eukaryotic / Multi antimicrobial extrusion protein / MatE
Similarity search - Domain/homology
Multidrug and toxin extrusion protein 1
Similarity search - Component
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.95 Å
AuthorsRomane K / Peteani G / Mukherjee S / Kowal J / Rossi L / Hou J / Kossiakoff A / Lemmin T / Locher KP
Funding support Switzerland, 2 items
OrganizationGrant numberCountry
Swiss National Science Foundation51NF40-185544 Switzerland
Swiss National Science Foundation214834 Switzerland
CitationJournal: Nat Commun / Year: 2025
Title: Structural basis of drug recognition by human MATE1 transporter.
Authors: Ksenija Romane / Giulia Peteani / Somnath Mukherjee / Julia Kowal / Lorenzo Rossi / Jingkai Hou / Anthony A Kossiakoff / Thomas Lemmin / Kaspar P Locher /
Abstract: Human MATE1 (multidrug and toxin extrusion protein 1) is highly expressed in the kidney and liver, where it mediates the final step in the excretion of a broad range of cationic drugs, including the ...Human MATE1 (multidrug and toxin extrusion protein 1) is highly expressed in the kidney and liver, where it mediates the final step in the excretion of a broad range of cationic drugs, including the antidiabetic drug metformin, into the urine and bile. This transport process is essential for drug clearance and also affects therapeutic efficacy. To understand the molecular basis of drug recognition by hMATE1, we determined cryo-electron microscopy structures of the transporter in complex with the substrates 1-methyl-4-phenylpyridinium (MPP) and metformin and with the inhibitor cimetidine. The structures reveal a shared binding site located in a negatively charged pocket in the C-lobe of the protein. We functionally validated key interactions using radioactivity-based cellular uptake assays using hMATE1 mutants. Molecular dynamics simulations provide insights into the different binding modes and dynamic behaviour of the ligands within the pocket. Collectively, these findings define the structural basis of hMATE1 substrate specificity and shed light on its role in drug transport and drug-drug interactions.
History
DepositionApr 26, 2025-
Header (metadata) releaseNov 5, 2025-
Map releaseNov 5, 2025-
UpdateNov 5, 2025-
Current statusNov 5, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_53508.png

Downloads & links

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Map

FileDownload / File: emd_53508.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.65 Å/pix.
x 448 pix.
= 291.2 Å		0.65 Å/pix.
x 448 pix.
= 291.2 Å		0.65 Å/pix.
x 448 pix.
= 291.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.65 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.113
Minimum - Maximum-0.19265956 - 0.36110467
Average (Standard dev.)-0.000050531482 (±0.0068082833)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions448448448
Spacing448448448
CellA=B=C: 291.19998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_53508_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_53508_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Human multidrug and toxin extrusion protein (MATE1) in complex wi...

EntireName: Human multidrug and toxin extrusion protein (MATE1) in complex with Fab
Components
  • Complex: Human multidrug and toxin extrusion protein (MATE1) in complex with Fab
    • Protein or peptide: Multidrug and toxin extrusion protein 1
    • Protein or peptide: Heavy chain of Fab
    • Protein or peptide: Light chain of Fab
  • Ligand: CHOLESTEROL
  • Ligand: water

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Supramolecule #1: Human multidrug and toxin extrusion protein (MATE1) in complex wi...

SupramoleculeName: Human multidrug and toxin extrusion protein (MATE1) in complex with Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 112 KDa

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Macromolecule #1: Multidrug and toxin extrusion protein 1

MacromoleculeName: Multidrug and toxin extrusion protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 61.967766 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MEAPEEPAPV RGGPEATLEV RGSRCLRLSA FREELRALLV LAGPAFLVQL MVFLISFISS VFCGHLGKLE LDAVTLAIAV INVTGVSVG FGLSSACDTL ISQTYGSQNL KHVGVILQRS ALVLLLCCFP CWALFLNTQH ILLLFRQDPD VSRLTQTYVT I FIPALPAT ...String:
MEAPEEPAPV RGGPEATLEV RGSRCLRLSA FREELRALLV LAGPAFLVQL MVFLISFISS VFCGHLGKLE LDAVTLAIAV INVTGVSVG FGLSSACDTL ISQTYGSQNL KHVGVILQRS ALVLLLCCFP CWALFLNTQH ILLLFRQDPD VSRLTQTYVT I FIPALPAT FLYMLQVKYL LNQGIVLPQI VTGVAANLVN ALANYLFLHQ LHLGVIGSAL ANLISQYTLA LLLFLYILGK KL HQATWGG WSLECLQDWA SFLRLAIPSM LMLCMEWWAY EVGSFLSGIL GMVELGAQSI VYELAIIVYM VPAGFSVAAS VRV GNALGA GDMEQARKSS TVSLLITVLF AVAFSVLLLS CKDHVGYIFT TDRDIINLVA QVVPIYAVSH LFEALACTSG GVLR GSGNQ KVGAIVNTIG YYVVGLPIGI ALMFATTLGV MGLWSGIIIC TVFQAVCFLG FIIQLNWKKA CQQAQVHANL KVNNV PRSG NSALPQDPLH PGCPENLEGI LTNDVGKTGE PQSDQQMRQE EPLPEHPQDG AKLSRKQLVL RRGLLLLGVF LILLVG ILV RFYVRIQ

UniProtKB: Multidrug and toxin extrusion protein 1

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Macromolecule #2: Heavy chain of Fab

MacromoleculeName: Heavy chain of Fab / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 24.249971 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: VQLVESGGGL VQPGGSLRLS CAASGFNFSY SYIHWVRQAP GKGLEWVASI SSYYGSTYYA DSVKGRFTIS ADTSKNTAYL QMNSLRAED TAVYYCARWA NTSSYGWRFW SNGLDYWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN ...String:
VQLVESGGGL VQPGGSLRLS CAASGFNFSY SYIHWVRQAP GKGLEWVASI SSYYGSTYYA DSVKGRFTIS ADTSKNTAYL QMNSLRAED TAVYYCARWA NTSSYGWRFW SNGLDYWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEPK

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Macromolecule #3: Light chain of Fab

MacromoleculeName: Light chain of Fab / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 23.140717 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QSYWWPLTFG QGTKVEIKRT VAAPSVFIFP PSDSQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QSYWWPLTFG QGTKVEIKRT VAAPSVFIFP PSDSQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNR

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Macromolecule #4: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 8 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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Macromolecule #5: water

MacromoleculeName: water / type: ligand / ID: 5 / Number of copies: 5 / 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

BufferpH: 7.4
VitrificationCryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 2 / Number real images: 9496 / Average electron dose: 53.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.6 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: cryoSPARC (ver. 4) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 327752
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4)
FSC plot (resolution estimation)

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