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- PDB-8hnd: Cryo-EM structure of human OATP1B1 in complex with estrone-3-sulfate -
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Open data
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Basic information
Entry | Database: PDB / ID: 8hnd | ||||||
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Title | Cryo-EM structure of human OATP1B1 in complex with estrone-3-sulfate | ||||||
![]() | Solute carrier organic anion transporter family member 1B1 | ||||||
![]() | MEMBRANE PROTEIN / transporter / OATP1B1 / organic anion transporting peptide | ||||||
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 / basal plasma membrane / Recycling of bile acids and salts / xenobiotic metabolic process / basolateral plasma membrane / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.19 Å | ||||||
![]() | Shan, Z. / Yang, X. / Liu, H. / Nan, J. / Yuan, Y. / Zhang, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures of human organic anion transporting polypeptide OATP1B1. Authors: Ziyang Shan / Xuemei Yang / Huihui Liu / Yafei Yuan / Yuan Xiao / Jing Nan / Wei Zhang / Wenqi Song / Jufang Wang / Feiwen Wei / Yanqing Zhang / ![]() Abstract: Members of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and ...Members of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and clinical drugs, such as bile salts, steroids, thyroid hormones, statins, antibiotics, antivirals, and anticancer drugs. OATP1B1 plays a vital role in transporting such substances into the liver for hepatic clearance. FDA and EMA recommend conducting in vitro testing of drug-drug interactions (DDIs) involving OATP1B1. However, the structure and working mechanism of OATPs still remains elusive. In this study, we determined cryo-EM structures of human OATP1B1 bound with representative endogenous metabolites (bilirubin and estrone-3-sulfate), a clinical drug (simeprevir), and a fluorescent indicator (2',7'-dichlorofluorescein), in both outward- and inward-open states. These structures reveal major and minor substrate binding pockets and conformational changes during transport. In combination with mutagenesis studies and molecular dynamics simulations, our work comprehensively elucidates the transport mechanism of OATP1B1 and provides the structural basis for DDI predictions involving OATP1B1, which will greatly promote our understanding of OATPs. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 113.1 KB | Display | ![]() |
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PDB format | ![]() | 83.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 34911MC ![]() 8hnbC ![]() 8hncC ![]() 8hnhC ![]() 8k6lC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 80330.312 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: estrone-3-sulfate / Source: (gene. exp.) ![]() ![]() |
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#2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#3: Chemical | ChemComp-FY5 / |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: OATP1B1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 9 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 2300 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: FEI FALCON IV (4k x 4k) |
EM imaging optics | Energyfilter name: TFS Selectris / Energyfilter slit width: 20 eV |
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Processing
EM software |
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CTF correction | Type: NONE | |||||||||
3D reconstruction | Resolution: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105261 / Symmetry type: POINT |