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- EMDB-16280: Cryo-EM structure of rat SLC22A6 bound to alpha-ketoglutaric acid -
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Open data
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Basic information
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Title | Cryo-EM structure of rat SLC22A6 bound to alpha-ketoglutaric acid | ||||||||||||
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![]() | membrane protein / transporter | ||||||||||||
Function / homology | ![]() 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 | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.53 Å | ||||||||||||
![]() | Parker JL / Kato T / Newstead S | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis for selective uptake and elimination of organic anions in the kidney by OAT1. Authors: Joanne L Parker / Takafumi Kato / Gabriel Kuteyi / Oleg Sitsel / Simon Newstead / ![]() ![]() Abstract: In mammals, the kidney plays an essential role in maintaining blood homeostasis through the selective uptake, retention or elimination of toxins, drugs and metabolites. Organic anion transporters ...In mammals, the kidney plays an essential role in maintaining blood homeostasis through the selective uptake, retention or elimination of toxins, drugs and metabolites. Organic anion transporters (OATs) are responsible for the recognition of metabolites and toxins in the nephron and their eventual urinary excretion. Inhibition of OATs is used therapeutically to improve drug efficacy and reduce nephrotoxicity. The founding member of the renal organic anion transporter family, OAT1 (also known as SLC22A6), uses the export of α-ketoglutarate (α-KG), a key intermediate in the Krebs cycle, to drive selective transport and is allosterically regulated by intracellular chloride. However, the mechanisms linking metabolite cycling, drug transport and intracellular chloride remain obscure. Here, we present cryogenic-electron microscopy structures of OAT1 bound to α-KG, the antiviral tenofovir and clinical inhibitor probenecid, used in the treatment of Gout. Complementary in vivo cellular assays explain the molecular basis for α-KG driven drug elimination and the allosteric regulation of organic anion transport in the kidney by chloride. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 85.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.7 KB 16.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.6 KB | Display | ![]() |
Images | ![]() | 40.8 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 84.7 MB 84.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8bw7MC ![]() 8bvrC ![]() 8bvsC ![]() 8bvtC ![]() 8omuC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #2
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Density Histograms |
-Half map: #1
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Sample components
-Entire : OAT1
Entire | Name: OAT1 |
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Components |
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-Supramolecule #1: OAT1
Supramolecule | Name: OAT1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-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: ![]() ![]() |
Molecular weight | Theoretical: 60.553559 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 QKQMMPLENL YFQ UniProtKB: Solute carrier family 22 member 6 |
-Macromolecule #2: Synthetic nanobody (Sybody)
Macromolecule | Name: Synthetic nanobody (Sybody) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 16.079819 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAGSSSQVQL VESGGGLVQA GGSLRLSCAA SGFPVKTEWM EWYRQAPGKE REWVAAIWSY GSGTRYADSV KGRFTISRDN AKNTVYLQM NSLKPEDTAV YYCLVRVGSW YHGQGTQVTV SAGRAGEQKL ISEEDLNSAV DHHHHHH |
-Macromolecule #3: 2-OXOGLUTARIC ACID
Macromolecule | Name: 2-OXOGLUTARIC ACID / type: ligand / ID: 3 / Number of copies: 1 / Formula: AKG |
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Molecular weight | Theoretical: 146.098 Da |
Chemical component information | ![]() ChemComp-AKG: |
-Macromolecule #4: CHLORIDE ION
Macromolecule | Name: CHLORIDE ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: CL |
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Molecular weight | Theoretical: 35.453 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-8bw7: |