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Open data
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Basic information
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Title | Human OATP1B1 | |||||||||
![]() | E1S-bound Human OATP1B1 with Fab18 | |||||||||
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![]() | organic anion / E1S / E-3-S / estrone-3-sulphate / SLCO1B1 / uptake / drug / transporter / polypeptide / liver / hepatocyte / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / thyroid hormone transmembrane transporter activity / bile acid transmembrane transporter activity / prostaglandin transmembrane transporter activity / organic anion transport / Atorvastatin ADME / organic anion transmembrane transporter activity ...Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / thyroid hormone transmembrane transporter activity / bile acid transmembrane transporter activity / prostaglandin 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 / basolateral plasma membrane / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 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 | ![]() | 367.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.3 KB 21.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 17.9 KB | Display | ![]() |
Images | ![]() | 110.8 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Others | ![]() ![]() | 391.9 MB 391.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 165.2 KB | Display | ![]() |
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Full document | ![]() | 164.8 KB | Display | |
Data in XML | ![]() | 496 B | Display | |
Data in CIF | ![]() | 373 B | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8phwMC ![]() 8pg0C 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 | E1S-bound Human OATP1B1 with Fab18 | ||||||||||||||||||||
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: E1S-bound Human OATP1B1 with Fab18 (half-map B)
File | emd_17677_half_map_1.map | ||||||||||||
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Annotation | E1S-bound Human OATP1B1 with Fab18 (half-map B) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: E1S-bound Human OATP1B1 with Fab18 (half-map A)
File | emd_17677_half_map_2.map | ||||||||||||
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Annotation | E1S-bound Human OATP1B1 with Fab18 (half-map A) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human OATP1B1
Entire | Name: Human OATP1B1 |
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Components |
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-Supramolecule #1: Human OATP1B1
Supramolecule | Name: Human OATP1B1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Theoretical: 180 KDa |
-Supramolecule #2: Solute carrier organic anion transporter family member 1B1
Supramolecule | Name: Solute carrier organic anion transporter family member 1B1 type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Fab18 (variable region)
Supramolecule | Name: Fab18 (variable region) / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Solute carrier organic anion transporter family member 1B1
Macromolecule | Name: Solute carrier organic anion transporter family member 1B1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 76.519438 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDQNQHLNKT AEAQPSENKK TRYCNGLKMF LAALSLSFIA KTLGAIIMKS SIIHIERRFE ISSSLVGFID GSFEIGNLLV IVFVSYFGS KLHRPKLIGI GCFIMGIGGV LTALPHFFMG YYRYSKETNI NSSENSTSTL STCLINQILS LNRASPEIVG K GCLKESGS ...String: MDQNQHLNKT AEAQPSENKK TRYCNGLKMF LAALSLSFIA KTLGAIIMKS SIIHIERRFE ISSSLVGFID GSFEIGNLLV IVFVSYFGS KLHRPKLIGI GCFIMGIGGV LTALPHFFMG YYRYSKETNI NSSENSTSTL STCLINQILS LNRASPEIVG K GCLKESGS YMWIYVFMGN MLRGIGETPI VPLGLSYIDD FAKEGHSSLY LGILNAIAMI GPIIGFTLGS LFSKMYVDIG YV DLSTIRI TPTDSRWVGA WWLNFLVSGL FSIISSIPFF FLPQTPNKPQ KERKASLSLH VLETNDEKDQ TANLTNQGKN ITK NVTGFF QSFKSILTNP LYVMFVLLTL LQVSSYIGAF TYVFKYVEQQ YGQPSSKANI LLGVITIPIF ASGMFLGGYI IKKF KLNTV GIAKFSCFTA VMSLSFYLLY FFILCENKSV AGLTMTYDGN NPVTSHRDVP LSYCNSDCNC DESQWEPVCG NNGIT YISP CLAGCKSSSG NKKPIVFYNC SCLEVTGLQN RNYSAHLGEC PRDDACTRKF YFFVAIQVLN LFFSALGGTS HVMLIV KIV QPELKSLALG FHSMVIRALG GILAPIYFGA LIDTTCIKWS TNNCGTRGSC RTYNSTSFSR VYLGLSSMLR VSSLVLY II LIYAMKKKYQ EKDINASENG SVMDEANLES LNKNKHFVPS AGADSETHC UniProtKB: Solute carrier organic anion transporter family member 1B1 |
-Macromolecule #2: Fab18 (heavy chain, variable region)
Macromolecule | Name: Fab18 (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: 24.374008 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSSSSIHWV RQAPGKGLEW VASISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARYGWGGPWY YWLRDSRSGI DYWGQGTLVT VSSASTKGPS VSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSSSSIHWV RQAPGKGLEW VASISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARYGWGGPWY YWLRDSRSGI DYWGQGTLVT VSSASTKGPS VSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSCDKT HT |
-Macromolecule #3: Fab18 (light chain, variable region)
Macromolecule | Name: Fab18 (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: estrone 3-sulfate
Macromolecule | Name: estrone 3-sulfate / type: ligand / ID: 4 / Number of copies: 1 / Formula: FY5 |
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Molecular weight | Theoretical: 350.429 Da |
Chemical component information | ![]() ChemComp-FY5: |
-Macromolecule #5: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 5 / Number of copies: 1 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.22 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 |