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- EMDB-4536: Nanodisc reconstituted Human-mouse chimeric ABCB1 (ABCB1HM)-EQ mu... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4536 | |||||||||
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Title | Nanodisc reconstituted Human-mouse chimeric ABCB1 (ABCB1HM)-EQ mutant in complex with UIC2 Fab and Zosuquidar. | |||||||||
![]() | Postprocessed map of human-mouse chimeric ABCB1 (ABCB1HM)- EQ mutant in complex with UIC2 fab and zosuquidar | |||||||||
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Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
![]() | Alam A | |||||||||
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 | ![]() | 228.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.6 KB 16.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.2 KB | Display | ![]() |
Images | ![]() | 66 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 294 KB | Display | ![]() |
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Full document | ![]() | 293.1 KB | Display | |
Data in XML | ![]() | 13.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6qeeMC ![]() 4539C ![]() 4540C ![]() 4541C ![]() 6qexC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Postprocessed map of human-mouse chimeric ABCB1 (ABCB1HM)- EQ mutant in complex with UIC2 fab and zosuquidar | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 ABCB1HM (human mouse chimeric ABCB1) EQ mu...
+Supramolecule #1: Nanodisc reconstituted ABCB1HM (human mouse chimeric ABCB1) EQ mu...
+Supramolecule #2: ABCB1HM
+Supramolecule #3: UIC2 Fab
+Macromolecule #1: ABCB1HM-EQ
+Macromolecule #2: UIC2 Antigen Binding Fragment Light chain
+Macromolecule #3: UIC2 Antigen Binding Fragment Heavy Chain
+Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #5: Zosuquidar
+Macromolecule #6: CHOLESTEROL
+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 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER |
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 |