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- PDB-8jxu: Cryo-EM structure of human ABC transporter ABCC2 under active tur... -
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Basic information
Entry | Database: PDB / ID: 8jxu | ||||||
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Title | Cryo-EM structure of human ABC transporter ABCC2 under active turnover condition | ||||||
![]() | ATP-binding cassette sub-family C member 2 | ||||||
![]() | TRANSPORT PROTEIN / ATP-dependent transporter / conjugated organic anions transporter / ATP hydrolyzes / bilirubin / ABC transporter | ||||||
Function / homology | ![]() Defective ABCC2 causes DJS / bilirubin transmembrane transporter activity / bilirubin transport / xenobiotic export from cell / leukotriene transport / ABC-type glutathione-S-conjugate transporter / ABC-type glutathione S-conjugate transporter activity / ATPase-coupled inorganic anion transmembrane transporter activity / xenobiotic transmembrane transport / Atorvastatin ADME ...Defective ABCC2 causes DJS / bilirubin transmembrane transporter activity / bilirubin transport / xenobiotic export from cell / leukotriene transport / ABC-type glutathione-S-conjugate transporter / ABC-type glutathione S-conjugate transporter activity / ATPase-coupled inorganic anion transmembrane transporter activity / xenobiotic transmembrane transport / Atorvastatin ADME / organic anion transmembrane transporter activity / heme catabolic process / xenobiotic transport across blood-brain barrier / transepithelial transport / intercellular canaliculus / ABC-type xenobiotic transporter / Paracetamol ADME / bile acid and bile salt transport / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / ABC-type xenobiotic transporter activity / Heme degradation / Aspirin ADME / xenobiotic transmembrane transporter activity / transport across blood-brain barrier / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / xenobiotic metabolic process / ABC-family proteins mediated transport / transmembrane transport / apical plasma membrane / negative regulation of gene expression / cell surface / ATP hydrolysis activity / ATP binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å | ||||||
![]() | Mao, Y.X. / Chen, Z.P. / Wang, L. / Hou, W.T. / Chen, Y.X. / Zhou, C.Z. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain. Authors: Yao-Xu Mao / Zhi-Peng Chen / Liang Wang / Jie Wang / Cong-Zhao Zhou / Wen-Tao Hou / Yuxing Chen / ![]() Abstract: Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including ...Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the cryo-electron microscopy, exhibiting a full transporter with a regulatory (R) domain inserted between the two half modules. Combined with substrate-stimulated ATPase and transport activity assays, structural analysis enables us to figure out transport cycle of ABCC2 with the R domain adopting various conformations. At the rest state, the R domain binding to the translocation cavity functions as an affinity filter that allows the substrates of high affinity to be transported in priority. Upon substrate binding, the R domain is expelled from the cavity and docks to the lateral of transmembrane domain following ATP hydrolysis. Our findings provide structural insights into a transport mechanism of ABC transporters finely tuned by the R domain. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 482.8 KB | Display | ![]() |
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PDB format | ![]() | 393.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 509.6 KB | Display | ![]() |
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Full document | ![]() | 523.3 KB | Display | |
Data in XML | ![]() | 27.8 KB | Display | |
Data in CIF | ![]() | 41.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36713MC ![]() 8jx7C ![]() 8jxqC ![]() 8jy4C ![]() 8jy5C 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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Components
#1: Protein | Mass: 176964.969 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: Q92887, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate, ABC-type xenobiotic transporter, ABC-type ...References: UniProt: Q92887, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate, ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter |
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#2: Chemical | ChemComp-ADP / |
#3: Chemical | ChemComp-ATP / |
#4: Chemical | ChemComp-MG / |
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: ATP-binding cassette sub-family C member 2 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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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 defocus max: 2000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.18.2_3874: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 131148 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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