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Open data
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Basic information
Entry | Database: PDB / ID: 6q81 | ||||||
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Title | Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state | ||||||
![]() | P-glycoprotein (ABCB1) | ||||||
![]() | MEMBRANE PROTEIN / P-glycoprotein / ABCB1 / ATP-binding cassette / transporter / protein structure | ||||||
Function / homology | ![]() hormone transport / cellular response to nonylphenol / cellular response to borneol / response to codeine / response to cyclosporin A / Atorvastatin ADME / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / negative regulation of sensory perception of pain ...hormone transport / cellular response to nonylphenol / cellular response to borneol / response to codeine / response to cyclosporin A / Atorvastatin ADME / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / negative regulation of sensory perception of pain / positive regulation of establishment of Sertoli cell barrier / regulation of intestinal absorption / cellular response to external biotic stimulus / response to quercetin / response to antineoplastic agent / Prednisone ADME / terpenoid transport / ceramide floppase activity / establishment of blood-retinal barrier / protein localization to bicellular tight junction / ceramide translocation / floppase activity / ABC-family proteins mediated transport / response to thyroxine / establishment of blood-brain barrier / phosphatidylethanolamine flippase activity / phosphatidylcholine floppase activity / xenobiotic transport across blood-brain barrier / intercellular canaliculus / xenobiotic detoxification by transmembrane export across the plasma membrane / cellular response to L-glutamate / response to vitamin A / export across plasma membrane / P-type phospholipid transporter / ABC-type xenobiotic transporter / response to glycoside / response to vitamin D / intestinal absorption / response to glucagon / response to alcohol / cellular response to antibiotic / ABC-type xenobiotic transporter activity / cellular hyperosmotic salinity response / phospholipid translocation / maintenance of blood-brain barrier / cellular response to alkaloid / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / response to cadmium ion / lactation / cellular response to dexamethasone stimulus / female pregnancy / placenta development / response to progesterone / cellular response to estradiol stimulus / brush border membrane / circadian rhythm / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / response to hypoxia / apical plasma membrane / response to xenobiotic stimulus / ATP hydrolysis activity / ATP binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7.9 Å | ||||||
![]() | Ford, R.C. / Thonghin, N. / Collins, R.F. / Barbieri, A. / Shafi, T. / Siebert, A. | ||||||
![]() | ![]() Title: Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 Å resolution. Authors: Nopnithi Thonghin / Richard F Collins / Alessandro Barbieri / Talha Shafi / Alistair Siebert / Robert C Ford / ![]() Abstract: BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. ...BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein. RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP ...RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being located between the NBDs and close to the Signature regions involved in cooperative NBD dimerization. This, and the gap-filling detergent suggest steric impediment to NBD dimerization in the post-hydrolytic state. Two central regions of density lie in two predicted drug-binding sites, implying that the protein may adventitiously bind hydrophobic substances even in the post-hydrolytic state. The previously unresolved N-terminal extension was observed, and the data suggests these 30 residues interact with the headgroup region of the lipid bilayer. CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked ...CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked to NBD dimerization, giving insights into the mechanism of drug-stimulation of P-glycoprotein activity. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 214.1 KB | Display | ![]() |
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PDB format | ![]() | 161 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 892.9 KB | Display | ![]() |
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Full document | ![]() | 929.2 KB | Display | |
Data in XML | ![]() | 43.6 KB | Display | |
Data in CIF | ![]() | 65 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4391MC ![]() 6gdiC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 140806.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: Chemical |
-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: P-glycoprotein trapped in the post-hydrolytic state. / Type: ORGANELLE OR CELLULAR COMPONENT / Details: ATP and Vanadate added / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 142 kDa/nm / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | 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 |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Method: SINGLE PARTICLE / Resolution: 7.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 135357 / Symmetry type: POINT |