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- PDB-7niw: Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posac... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7niw | ||||||||||||
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Title | Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posaconazole-bound, inward-open conformation) | ||||||||||||
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![]() | PROTEIN TRANSPORT / ABCB4 / MDR3 / nanodisc / lipid transporter / transporter / phosphatidylcholine | ||||||||||||
Function / homology | ![]() response to fenofibrate / Defective ABCB4 causes PFIC3, ICP3 and GBD1 / positive regulation of phospholipid transport / positive regulation of cholesterol transport / positive regulation of phospholipid translocation / bile acid secretion / phospholipid transporter activity / cellular response to bile acid / phosphatidylcholine floppase activity / intercellular canaliculus ...response to fenofibrate / Defective ABCB4 causes PFIC3, ICP3 and GBD1 / positive regulation of phospholipid transport / positive regulation of cholesterol transport / positive regulation of phospholipid translocation / bile acid secretion / phospholipid transporter activity / cellular response to bile acid / phosphatidylcholine floppase activity / intercellular canaliculus / lipid homeostasis / P-type phospholipid transporter / phospholipid translocation / clathrin-coated vesicle / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / lipid metabolic process / PPARA activates gene expression / ABC-family proteins mediated transport / transmembrane transport / apical plasma membrane / membrane raft / focal adhesion / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||
![]() | Nosol, K. / Locher, K.P. | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structures of ABCB4 provide insight into phosphatidylcholine translocation. Authors: Kamil Nosol / Rose Bang-Sørensen / Rossitza N Irobalieva / Satchal K Erramilli / Bruno Stieger / Anthony A Kossiakoff / Kaspar P Locher / ![]() ![]() Abstract: ABCB4 is expressed in hepatocytes and translocates phosphatidylcholine into bile canaliculi. The mechanism of specific lipid recruitment from the canalicular membrane, which is essential to mitigate ...ABCB4 is expressed in hepatocytes and translocates phosphatidylcholine into bile canaliculi. The mechanism of specific lipid recruitment from the canalicular membrane, which is essential to mitigate the cytotoxicity of bile salts, is poorly understood. We present cryogenic electron microscopy structures of human ABCB4 in three distinct functional conformations. An apo-inward structure reveals how phospholipid can be recruited from the inner leaflet of the membrane without flipping its orientation. An occluded structure reveals a single phospholipid molecule in a central cavity. Its choline moiety is stabilized by cation-π interactions with an essential tryptophan residue, rationalizing the specificity of ABCB4 for phosphatidylcholine. In an inhibitor-bound structure, a posaconazole molecule blocks phospholipids from reaching the central cavity. Using a proteoliposome-based translocation assay with fluorescently labeled phosphatidylcholine analogs, we recapitulated the substrate specificity of ABCB4 in vitro and confirmed the role of the key tryptophan residue. Our results provide a structural basis for understanding an essential translocation step in the generation of bile and its sensitivity to azole drugs. | ||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 282.5 KB | Display | ![]() |
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PDB format | ![]() | 233 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 65.2 KB | Display | |
Data in CIF | ![]() | 95.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 12367MC ![]() 7niuC ![]() 7nivC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 140833.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P21439, P-type phospholipid transporter |
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-Antibody , 2 types, 2 molecules BC
#2: Antibody | Mass: 23346.957 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Antibody | Mass: 25754.572 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 3 types, 8 molecules ![](data/chem/img/CLR.gif)
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#4: Chemical | ChemComp-CLR / #5: Chemical | ChemComp-X2N / | #6: Chemical | ChemComp-DLP / | |
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-Details
Has ligand of interest | Y |
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-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
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Specimen | Conc.: 0.48 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | 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 / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 80.4 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 90891 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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