+Open data
-Basic information
Entry | Database: PDB / ID: 6q81 | ||||||
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Title | Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state | ||||||
Components | P-glycoprotein (ABCB1) | ||||||
Keywords | MEMBRANE PROTEIN / P-glycoprotein / ABCB1 / ATP-binding cassette / transporter / protein structure | ||||||
Function / homology | Function and homology information hormone transport / 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 / response to quercetin / negative regulation of sensory perception of pain ...hormone transport / 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 / response to quercetin / negative regulation of sensory perception of pain / regulation of intestinal absorption / cellular response to external biotic stimulus / response to antineoplastic agent / positive regulation of establishment of Sertoli cell barrier / Prednisone ADME / terpenoid transport / ceramide floppase activity / response to glycoside / ceramide translocation / floppase activity / establishment of blood-retinal barrier / protein localization to bicellular tight junction / response to alcohol / ABC-family proteins mediated transport / phosphatidylethanolamine flippase activity / response to thyroxine / establishment of blood-brain barrier / phosphatidylcholine floppase activity / xenobiotic transport across blood-brain barrier / export across plasma membrane / ABC-type xenobiotic transporter / xenobiotic detoxification by transmembrane export across the plasma membrane / cellular response to L-glutamate / intercellular canaliculus / P-type phospholipid transporter / response to vitamin D / ABC-type xenobiotic transporter activity / response to vitamin A / intestinal absorption / response to glucagon / phospholipid translocation / cellular response to antibiotic / cellular hyperosmotic salinity response / maintenance of blood-brain barrier / cellular response to alkaloid / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / transmembrane transporter activity / response to cadmium ion / lactation / cellular response to dexamethasone stimulus / cellular response to estradiol stimulus / response to progesterone / female pregnancy / brush border membrane / placenta development / circadian rhythm / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / response to hypoxia / response to xenobiotic stimulus / apical plasma membrane / ATP hydrolysis activity / ATP binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7.9 Å | ||||||
Authors | Ford, R.C. / Thonghin, N. / Collins, R.F. / Barbieri, A. / Shafi, T. / Siebert, A. | ||||||
Citation | Journal: BMC Struct Biol / Year: 2018 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. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
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PDBx/mmCIF format | 6q81.cif.gz | 214.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6q81.ent.gz | 161 KB | Display | PDB format |
PDBx/mmJSON format | 6q81.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6q81_validation.pdf.gz | 892.9 KB | Display | wwPDB validaton report |
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Full document | 6q81_full_validation.pdf.gz | 929.2 KB | Display | |
Data in XML | 6q81_validation.xml.gz | 43.6 KB | Display | |
Data in CIF | 6q81_validation.cif.gz | 65 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/q8/6q81 ftp://data.pdbj.org/pub/pdb/validation_reports/q8/6q81 | HTTPS FTP |
-Related structure data
Related structure data | 4391MC 6gdiC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-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.) Mus musculus (house mouse) / Production host: Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: P21447 |
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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 |
-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: Mus musculus (house mouse) |
Source (recombinant) | Organism: Saccharomyces cerevisiae (brewer's yeast) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-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 |