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Yorodumi- EMDB-40355: Structure of rat organic anion transporter 1 (OAT1) in complex wi... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40355 | |||||||||
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Title | Structure of rat organic anion transporter 1 (OAT1) in complex with probenecid | |||||||||
Map data | ||||||||||
Sample |
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Keywords | organic anion transporter / OAT / SLC22 / drug transporter / probenecid / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information Organic anion transport / renal tubular secretion / alpha-ketoglutarate transmembrane transporter activity / alpha-ketoglutarate transport / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / metanephric proximal tubule development / prostaglandin transport / prostaglandin transmembrane transporter activity / organic anion transport ...Organic anion transport / renal tubular secretion / alpha-ketoglutarate transmembrane transporter activity / alpha-ketoglutarate transport / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / metanephric proximal tubule development / prostaglandin transport / prostaglandin transmembrane transporter activity / organic anion transport / organic anion transmembrane transporter activity / solute:inorganic anion antiporter activity / monoatomic anion transport / antiporter activity / chloride ion binding / xenobiotic transmembrane transporter activity / transmembrane transporter activity / basal plasma membrane / caveola / response to organic cyclic compound / transmembrane transport / basolateral plasma membrane / protein-containing complex / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.86 Å | |||||||||
Authors | Dou T / Jiang J | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2023 Title: The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM. Authors: Tongyi Dou / Tengfei Lian / Shi Shu / Yi He / Jiansen Jiang / Abstract: Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug ...Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug interactions. In the kidneys, OATs facilitate the elimination of metabolic waste products and xenobiotics. However, their transport activities can lead to the accumulation of certain toxic compounds within cells, causing kidney damage. Moreover, OATs are important drug targets, because their inhibition modulates the elimination or retention of substrates linked to diseases. Despite extensive research on OATs, the molecular basis of their substrate and inhibitor binding remains poorly understood. Here we report the cryo-EM structures of rat OAT1 (also known as SLC22A6) and its complexes with para-aminohippuric acid and probenecid at 2.1, 2.8 and 2.9 Å resolution, respectively. Our findings reveal a highly conserved substrate binding mechanism for SLC22 transporters, wherein four aromatic residues form a cage to accommodate the polyspecific binding of diverse compounds. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40355.map.gz | 14.3 MB | EMDB map data format | |
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Header (meta data) | emd-40355-v30.xml emd-40355.xml | 16.1 KB 16.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40355_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_40355.png | 81.5 KB | ||
Masks | emd_40355_msk_1.map | 15.6 MB | Mask map | |
Filedesc metadata | emd-40355.cif.gz | 5.9 KB | ||
Others | emd_40355_half_map_1.map.gz emd_40355_half_map_2.map.gz | 14.5 MB 14.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40355 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40355 | HTTPS FTP |
-Validation report
Summary document | emd_40355_validation.pdf.gz | 913.4 KB | Display | EMDB validaton report |
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Full document | emd_40355_full_validation.pdf.gz | 913 KB | Display | |
Data in XML | emd_40355_validation.xml.gz | 14.7 KB | Display | |
Data in CIF | emd_40355_validation.cif.gz | 19.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40355 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40355 | HTTPS FTP |
-Related structure data
Related structure data | 8sdzMC 8sduC 8sdyC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_40355.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_40355_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_40355_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_40355_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Rat OAT1/probenecid complex solubilized in detergent LMNG
Entire | Name: Rat OAT1/probenecid complex solubilized in detergent LMNG |
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Components |
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-Supramolecule #1: Rat OAT1/probenecid complex solubilized in detergent LMNG
Supramolecule | Name: Rat OAT1/probenecid complex solubilized in detergent LMNG type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 61 KDa |
-Macromolecule #1: Solute carrier family 22 member 6
Macromolecule | Name: Solute carrier family 22 member 6 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 60.816836 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR PPANANLSKD GGLEAWLPLD KQGQPESCLR FTSPQWGPP FYNGTEANGT RVTEPCIDGW VYDNSTFPST IVTEWNLVCS HRAFRQLAQS LYMVGVLLGA MVFGYLADRL G RRKVLILN ...String: MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR PPANANLSKD GGLEAWLPLD KQGQPESCLR FTSPQWGPP FYNGTEANGT RVTEPCIDGW VYDNSTFPST IVTEWNLVCS HRAFRQLAQS LYMVGVLLGA MVFGYLADRL G RRKVLILN YLQTAVSGTC AAYAPNYTVY CVFRLLSGMS LASIAINCMT LNVEWMPIHT RAYVGTLIGY VYSLGQFLLA GI AYAVPHW RHLQLVVSVP FFIAFIYSWF FIESARWYSS SGRLDLTLRA LQRVARINGK QEEGAKLSIE VLRTSLQKEL TLS KGQASA MELLRCPTLR HLFLCLSMLW FATSFAYYGL VMDLQGFGVS MYLIQVIFGA VDLPAKFVCF LVINSMGRRP AQMA SLLLA GICILVNGII PKSHTIIRTS LAVLGKGCLA SSFNCIFLYT GELYPTVIRQ TGLGMGSTMA RVGSIVSPLV SMTAE FYPS MPLFIFGAVP VVASAVTALL PETLGQPLPD TVQDLKSRSR GKQNQQQQEQ QKQMMPLQAS TQEKNGL UniProtKB: Solute carrier family 22 member 6 |
-Macromolecule #2: 4-(dipropylsulfamoyl)benzoic acid
Macromolecule | Name: 4-(dipropylsulfamoyl)benzoic acid / type: ligand / ID: 2 / Number of copies: 1 / Formula: RTO |
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Molecular weight | Theoretical: 285.359 Da |
Chemical component information | ChemComp-RTO: |
-Macromolecule #3: water
Macromolecule | Name: water / type: ligand / ID: 3 / Number of copies: 22 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 Details: TBS buffer (20 mM Tris-HCl, 150 mM NaCl, pH 8.0) with 0.01% LMNG |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 4160 / Average exposure time: 6.25 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-8sdz: |