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Yorodumi- EMDB-4541: Nanodisc reconstituted human ABCB1 in complex with UIC2 fab and taxol -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4541 | |||||||||
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Title | Nanodisc reconstituted human ABCB1 in complex with UIC2 fab and taxol | |||||||||
Map data | postprocessed map of human ABCB1 in complex with UIC2 fab and taxol after partial nanodisc signal subtraction. | |||||||||
Sample |
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Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Alam A / Locher KP | |||||||||
Citation | Journal: Science / Year: 2019 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 |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4541.map.gz | 224.1 MB | EMDB map data format | |
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Header (meta data) | emd-4541-v30.xml emd-4541.xml | 10.6 KB 10.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4541_fsc.xml | 14.2 KB | Display | FSC data file |
Images | emd_4541.png | 140.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4541 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4541 | HTTPS FTP |
-Validation report
Summary document | emd_4541_validation.pdf.gz | 259.7 KB | Display | EMDB validaton report |
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Full document | emd_4541_full_validation.pdf.gz | 258.8 KB | Display | |
Data in XML | emd_4541_validation.xml.gz | 13.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4541 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4541 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_4541.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | postprocessed map of human ABCB1 in complex with UIC2 fab and taxol after partial nanodisc signal subtraction. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Sample components
-Entire : Nanodisc reconstituted ABCB1HM (human mouse chimeric ABCB1) EQ mu...
Entire | Name: Nanodisc reconstituted ABCB1HM (human mouse chimeric ABCB1) EQ mutant in complex with UIC2 Fab and zosuquidar |
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Components |
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-Supramolecule #1: Nanodisc reconstituted ABCB1HM (human mouse chimeric ABCB1) EQ mu...
Supramolecule | Name: Nanodisc reconstituted ABCB1HM (human mouse chimeric ABCB1) EQ mutant in complex with UIC2 Fab and zosuquidar type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Molecular weight | Experimental: 200 KDa |
-Supramolecule #2: nanodisc reconstituted human ABCB1 in complex with UIC2 Fab and taxol
Supramolecule | Name: nanodisc reconstituted human ABCB1 in complex with UIC2 Fab and taxol type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: UIC2 Fab
Supramolecule | Name: UIC2 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |