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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Human OATP1B3 | |||||||||
![]() | bicarbonate-bound OATP1B3 with Fab19 | |||||||||
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![]() | organic anion / bicarbonate / SLCO1B3 / uptake / drug / transporter / polypeptide / liver / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() Defective SLCO1B3 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / negative regulation of peptidase activity / bile acid transmembrane transporter activity / organic anion transport / Atorvastatin ADME / organic anion transmembrane transporter activity / heme catabolic process ...Defective SLCO1B3 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / negative regulation of peptidase activity / bile acid transmembrane transporter activity / organic anion transport / Atorvastatin ADME / organic anion transmembrane transporter activity / heme catabolic process / bile acid and bile salt transport / Heme degradation / monoatomic ion transport / Recycling of bile acids and salts / xenobiotic metabolic process / basal plasma membrane / serine-type endopeptidase inhibitor activity / basolateral plasma membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.97 Å | |||||||||
![]() | Ciuta A-D / Nosol K / Kowal J / Mukherjee S / Ramirez AS / Stieger B / Kossiakoff AA / Locher KP | |||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structure of human drug transporters OATP1B1 and OATP1B3. Authors: Anca-Denise Ciută / Kamil Nosol / Julia Kowal / Somnath Mukherjee / Ana S Ramírez / Bruno Stieger / Anthony A Kossiakoff / Kaspar P Locher / ![]() ![]() Abstract: The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug ...The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug elimination from the human body. Polymorphic variants of these transporters can cause reduced drug clearance and adverse drug effects such as statin-induced rhabdomyolysis, and co-administration of OATP substrates can lead to damaging drug-drug interaction. Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 316.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 18.2 KB | Display | ![]() |
Images | ![]() | 96.4 KB | ||
Others | ![]() ![]() | 314.6 MB 315.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8pg0MC ![]() 8phwC 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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Annotation | bicarbonate-bound OATP1B3 with Fab19 | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.51 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: bicarbonate-bound OATP1B3 with Fab19 (half-map 1)
File | emd_17655_half_map_1.map | ||||||||||||
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Annotation | bicarbonate-bound OATP1B3 with Fab19 (half-map 1) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: bicarbonate-bound OATP1B3 with Fab19 (half-map 2)
File | emd_17655_half_map_2.map | ||||||||||||
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Annotation | bicarbonate-bound OATP1B3 with Fab19 (half-map 2) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human OATP1B3
Entire | Name: Human OATP1B3 |
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Components |
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-Supramolecule #1: Human OATP1B3
Supramolecule | Name: Human OATP1B3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 180 KDa |
-Macromolecule #1: Solute carrier organic anion transporter family member 1B3
Macromolecule | Name: Solute carrier organic anion transporter family member 1B3 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 77.478586 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDQHQHLNKT AESASSEKKK TRRCNGFKMF LAALSFSYIA KALGGIIMKI SITQIERRFD ISSSLAGLID GSFEIGNLLV IVFVSYFGS KLHRPKLIGI GCLLMGTGSI LTSLPHFFMG YYRYSKETHI NPSENSTSSL STCLINQTLS FNGTSPEIVE K DCVKESGS ...String: MDQHQHLNKT AESASSEKKK TRRCNGFKMF LAALSFSYIA KALGGIIMKI SITQIERRFD ISSSLAGLID GSFEIGNLLV IVFVSYFGS KLHRPKLIGI GCLLMGTGSI LTSLPHFFMG YYRYSKETHI NPSENSTSSL STCLINQTLS FNGTSPEIVE K DCVKESGS HMWIYVFMGN MLRGIGETPI VPLGISYIDD FAKEGHSSLY LGSLNAIGMI GPVIGFALGS LFAKMYVDIG YV DLSTIRI TPKDSRWVGA WWLGFLVSGL FSIISSIPFF FLPKNPNKPQ KERKISLSLH VLKTNDDRNQ TANLTNQGKN VTK NVTGFF QSLKSILTNP LYVIFLLLTL LQVSSFIGSF TYVFKYMEQQ YGQSASHANF LLGIITIPTV ATGMFLGGFI IKKF KLSLV GIAKFSFLTS MISFLFQLLY FPLICESKSV AGLTLTYDGN NSVASHVDVP LSYCNSECNC DESQWEPVCG NNGIT YLSP CLAGCKSSSG IKKHTVFYNC SCVEVTGLQN RNYSAHLGEC PRDNTCTRKF FIYVAIQVIN SLFSATGGTT FILLTV KIV QPELKALAMG FQSMVIRTLG GILAPIYFGA LIDKTCMKWS TNSCGAQGAC RIYNSVFFGR VYLGLSIALR FPALVLY IV FIFAMKKKFQ GKDTKASDNE RKVMDEANLE FLNNGEHFVP SAGTDSKTCN LDMQDNAAAN UniProtKB: Solute carrier organic anion transporter family member 1B3 |
-Macromolecule #2: Fab19 (heavy chain, variable region)
Macromolecule | Name: Fab19 (heavy chain, variable region) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.599549 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSSSSIHWV RQAPGKGLEW VASISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARYYIKRWWL MSWEDYSMGL DYWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSSSSIHWV RQAPGKGLEW VASISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARYYIKRWWL MSWEDYSMGL DYWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC L VKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSCDKT HT |
-Macromolecule #3: Fab19 (light chain, variable region)
Macromolecule | Name: Fab19 (light chain, variable region) / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.258783 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSSSSLITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSSSSLITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #5: BICARBONATE ION
Macromolecule | Name: BICARBONATE ION / type: ligand / ID: 5 / Number of copies: 1 / Formula: BCT |
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Molecular weight | Theoretical: 61.017 Da |
Chemical component information | ![]() ChemComp-BCT: |
-Macromolecule #6: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 6 / Number of copies: 3 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.59 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |