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- EMDB-4539: Nanodisc reconstituted human ABCB1 in complex with UIC2 fab and taxol -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4539 | |||||||||
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Title | Nanodisc reconstituted human ABCB1 in complex with UIC2 fab and taxol | |||||||||
![]() | Postprocessed map of nanodisc reconstituted human ABCB1 in complex with UIC2 Fab and taxol | |||||||||
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Function / homology | ![]() positive regulation of anion channel activity / carboxylic acid transmembrane transport / carboxylic acid transmembrane transporter activity / terpenoid transport / ceramide floppase activity / regulation of response to osmotic stress / floppase activity / Abacavir transmembrane transport / ceramide translocation / external side of apical plasma membrane ...positive regulation of anion channel activity / carboxylic acid transmembrane transport / carboxylic acid transmembrane transporter activity / terpenoid transport / ceramide floppase activity / regulation of response to osmotic stress / floppase activity / Abacavir transmembrane transport / ceramide translocation / external side of apical plasma membrane / Atorvastatin ADME / phosphatidylethanolamine flippase activity / xenobiotic transport across blood-brain barrier / phosphatidylcholine floppase activity / transepithelial transport / xenobiotic detoxification by transmembrane export across the plasma membrane / export across plasma membrane / ABC-type xenobiotic transporter / P-type phospholipid transporter / ABC-type xenobiotic transporter activity / phospholipid translocation / Prednisone ADME / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / transmembrane transporter activity / transport across blood-brain barrier / ATPase-coupled transmembrane transporter activity / xenobiotic metabolic process / regulation of chloride transport / stem cell proliferation / ABC-family proteins mediated transport / transmembrane transport / G2/M transition of mitotic cell cycle / response to xenobiotic stimulus / apical plasma membrane / ubiquitin protein ligase binding / cell surface / ATP hydrolysis activity / extracellular exosome / ATP binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
![]() | Alam A / Locher KP | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insight into substrate and inhibitor discrimination by human P-glycoprotein. Authors: Amer Alam / Julia Kowal / Eugenia Broude / Igor Roninson / Kaspar P Locher / ![]() ![]() Abstract: ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic ...ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic drug delivery. We determined the 3.5-angstrom cryo-electron microscopy structure of substrate-bound human ABCB1 reconstituted in lipidic nanodiscs, revealing a single molecule of the chemotherapeutic compound paclitaxel (Taxol) bound in a central, occluded pocket. A second structure of inhibited, human-mouse chimeric ABCB1 revealed two molecules of zosuquidar occupying the same drug-binding pocket. Minor structural differences between substrate- and inhibitor-bound ABCB1 sites are amplified toward the nucleotide-binding domains (NBDs), revealing how the plasticity of the drug-binding site controls the dynamics of the adenosine triphosphate-hydrolyzing NBDs. Ordered cholesterol and phospholipid molecules suggest how the membrane modulates the conformational changes associated with drug binding and transport. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 227.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.9 KB 15.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.2 KB | Display | ![]() |
Images | ![]() | 72.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6qexMC ![]() 4536C ![]() 4540C ![]() 4541C ![]() 6qeeC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Postprocessed map of nanodisc reconstituted human ABCB1 in complex with UIC2 Fab and taxol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : Nanodisc reconstituted human ABCB1 in complex with UIC2 Fab and taxol
+Supramolecule #1: Nanodisc reconstituted human ABCB1 in complex with UIC2 Fab and taxol
+Supramolecule #2: nanodisc reconstituted human ABCB1
+Supramolecule #3: UIC2 Fab
+Macromolecule #1: Multidrug resistance protein 1
+Macromolecule #2: UIC2 Fab lightchain
+Macromolecule #3: UIC2 Fab heavy chain
+Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #5: CHOLESTEROL
+Macromolecule #6: TAXOL
+Macromolecule #7: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 2.1 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |