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Yorodumi- PDB-5uak: Dephosphorylated, ATP-free human cystic fibrosis transmembrane co... -
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-Basic information
Entry | Database: PDB / ID: 5uak | |||||||||
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Title | Dephosphorylated, ATP-free human cystic fibrosis transmembrane conductance regulator (CFTR) | |||||||||
Components | (Cystic fibrosis transmembrane conductance regulator) x 2 | |||||||||
Keywords | MEMBRANE PROTEIN / HYDROLASE / ABC transporter / anion channel / cystic fibrosis | |||||||||
Function / homology | Function and homology information positive regulation of voltage-gated chloride channel activity / positive regulation of cyclic nucleotide-gated ion channel activity / Sec61 translocon complex binding / channel-conductance-controlling ATPase / intracellularly ATP-gated chloride channel activity / positive regulation of enamel mineralization / transepithelial water transport / RHO GTPases regulate CFTR trafficking / intracellular pH elevation / amelogenesis ...positive regulation of voltage-gated chloride channel activity / positive regulation of cyclic nucleotide-gated ion channel activity / Sec61 translocon complex binding / channel-conductance-controlling ATPase / intracellularly ATP-gated chloride channel activity / positive regulation of enamel mineralization / transepithelial water transport / RHO GTPases regulate CFTR trafficking / intracellular pH elevation / amelogenesis / chloride channel inhibitor activity / ATPase-coupled inorganic anion transmembrane transporter activity / Golgi-associated vesicle membrane / multicellular organismal-level water homeostasis / cholesterol transport / membrane hyperpolarization / vesicle docking involved in exocytosis / bicarbonate transport / bicarbonate transmembrane transporter activity / chloride channel regulator activity / chloride transmembrane transporter activity / sperm capacitation / chloride channel activity / cholesterol biosynthetic process / RHOQ GTPase cycle / positive regulation of exocytosis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / chloride channel complex / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / cellular response to cAMP / cellular response to forskolin / chloride transmembrane transport / response to endoplasmic reticulum stress / isomerase activity / clathrin-coated endocytic vesicle membrane / establishment of localization in cell / PDZ domain binding / Defective CFTR causes cystic fibrosis / Late endosomal microautophagy / ABC-family proteins mediated transport / recycling endosome / transmembrane transport / Aggrephagy / Chaperone Mediated Autophagy / recycling endosome membrane / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / early endosome membrane / protein-folding chaperone binding / endosome membrane / early endosome / Ub-specific processing proteases / apical plasma membrane / lysosomal membrane / endoplasmic reticulum membrane / enzyme binding / cell surface / ATP hydrolysis activity / protein-containing complex / ATP binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.87 Å | |||||||||
Authors | Liu, F. / Zhang, Z. / Chen, J. | |||||||||
Citation | Journal: Cell / Year: 2017 Title: Molecular Structure of the Human CFTR Ion Channel. Authors: Fangyu Liu / Zhe Zhang / László Csanády / David C Gadsby / Jue Chen / Abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of ...The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening. By analyzing the sigmoid time course of CFTR current activation, we propose that PKA phosphorylation of the R domain is enabled by its infrequent spontaneous disengagement, which also explains residual ATPase and gating activity of dephosphorylated CFTR. From comparison with MRP1, a feature distinguishing CFTR from all other ABC transporters is the helix-loop transition in transmembrane helix 8, which likely forms the structural basis for CFTR's channel function. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 5uak.cif.gz | 243.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5uak.ent.gz | 191.2 KB | Display | PDB format |
PDBx/mmJSON format | 5uak.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5uak_validation.pdf.gz | 838.4 KB | Display | wwPDB validaton report |
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Full document | 5uak_full_validation.pdf.gz | 839.4 KB | Display | |
Data in XML | 5uak_validation.xml.gz | 33.6 KB | Display | |
Data in CIF | 5uak_validation.cif.gz | 51.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ua/5uak ftp://data.pdbj.org/pub/pdb/validation_reports/ua/5uak | HTTPS FTP |
-Related structure data
Related structure data | 8516M M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 169353.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CFTR, ABCC7 / Cell line (production host): HEK293S GnTI- / Production host: Homo sapiens (human) / References: UniProt: P13569, EC: 3.6.3.49 |
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#2: Protein/peptide | Mass: 1635.006 Da / Num. of mol.: 1 / Fragment: R domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CFTR, ABCC7 / Cell line (production host): HEK293S GnTI- / Production host: Homo sapiens (human) |
-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: human cystic fibrosis transmembrane conductance regulator (CFTR) Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 168 kDa/nm / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293S GnTI- / Plasmid: BacMam |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK I / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K |
-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: 1.68 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.87 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 415915 / Symmetry type: POINT |