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- PDB-7p06: Cryo-EM structure of Pdr5 from Saccharomyces cerevisiae in outwar... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7p06 | ||||||
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Title | Cryo-EM structure of Pdr5 from Saccharomyces cerevisiae in outward-facing conformation with ADP-orthovanadate/ATP | ||||||
![]() | Pleiotropic ABC efflux transporter of multiple drugs | ||||||
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Function / homology | ![]() intracellular monoatomic cation homeostasis / xenobiotic detoxification by transmembrane export across the plasma membrane / ABC-type xenobiotic transporter activity / response to cycloheximide / cell periphery / response to xenobiotic stimulus / response to antibiotic / ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Szewczak-Harris, A. / Wagner, M. / Du, D. / Schmitt, L. / Luisi, B.F. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5. Authors: Andrzej Harris / Manuel Wagner / Dijun Du / Stefanie Raschka / Lea-Marie Nentwig / Holger Gohlke / Sander H J Smits / Ben F Luisi / Lutz Schmitt / ![]() ![]() ![]() Abstract: Pdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux ...Pdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux through uncoupled hydrolysis of nucleotides, enabling organisms such as baker's yeast and pathogenic fungi to survive in the presence of chemically diverse antifungal agents. Here, we present the molecular structure of Pdr5 solved with single particle cryo-EM, revealing details of an ATP-driven conformational cycle, which mechanically drives drug translocation through an amphipathic channel, and a clamping switch within a conserved linker loop that acts as a nucleotide sensor. One half of the transporter remains nearly invariant throughout the cycle, while its partner undergoes changes that are transmitted across inter-domain interfaces to support a peristaltic motion of the pumped molecule. The efflux model proposed here rationalises the pleiotropic impact of Pdr5 and opens new avenues for the development of effective antifungal compounds. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 450.4 KB | Display | ![]() |
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PDB format | ![]() | 380.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 13145MC ![]() 7p03C ![]() 7p04C ![]() 7p05C 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: 170617.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: ATCC 204508 / S288c / References: UniProt: P33302 |
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#2: Chemical | ChemComp-ATP / ![]() |
#3: Chemical | ChemComp-MG / |
#4: Chemical | ChemComp-AOV / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Cryo-EM structure of Pdr5 from Saccharomyces cerevisiae in outward-facing conformation with ADP-orthovanadate/ATP Type: COMPLEX / Entity ID: #1 / Source: NATURAL | |||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||
Source (natural) | Organism: ![]() ![]() ![]() | |||||||||||||||
Buffer solution | pH: 7.8 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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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![]() ![]() |
Specimen holder | Cryogen: HELIUM / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 1.31 sec. / Electron dose: 48.13 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
EM imaging optics | Energyfilter slit width: 20 eV |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.77 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 55155 / Algorithm: BACK PROJECTION / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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