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Yorodumi- PDB-5njg: Structure of an ABC transporter: part of the structure that could... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5njg | |||||||||
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Title | Structure of an ABC transporter: part of the structure that could be built de novo | |||||||||
Components |
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Keywords | TRANSPORT PROTEIN / ABC transporter | |||||||||
Function / homology | Function and homology information biotin transmembrane transporter activity / biotin transport / riboflavin transport / riboflavin transmembrane transporter activity / renal urate salt excretion / urate transmembrane transporter activity / urate metabolic process / Abacavir transmembrane transport / external side of apical plasma membrane / organic anion transport ...biotin transmembrane transporter activity / biotin transport / riboflavin transport / riboflavin transmembrane transporter activity / renal urate salt excretion / urate transmembrane transporter activity / urate metabolic process / Abacavir transmembrane transport / external side of apical plasma membrane / organic anion transport / organic anion transmembrane transporter activity / xenobiotic transport across blood-brain barrier / export across plasma membrane / ABC-type xenobiotic transporter / Paracetamol ADME / Ciprofloxacin ADME / transepithelial transport / ABC-type xenobiotic transporter activity / cellular detoxification / NFE2L2 regulating MDR associated enzymes / Heme biosynthesis / Heme degradation / lipid transport / xenobiotic transmembrane transporter activity / efflux transmembrane transporter activity / transport across blood-brain barrier / ATPase-coupled transmembrane transporter activity / mitochondrial membrane / brush border membrane / Iron uptake and transport / transmembrane transport / apical plasma membrane / membrane raft / ATP hydrolysis activity / protein homodimerization activity / nucleoplasm / ATP binding / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.78 Å | |||||||||
Authors | Taylor, N.M.I. / Manolaridis, I. / Jackson, S.M. / Kowal, J. / Stahlberg, H. / Locher, K.P. | |||||||||
Funding support | Switzerland, 2items
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Citation | Journal: Nature / Year: 2017 Title: Structure of the human multidrug transporter ABCG2. Authors: Nicholas M I Taylor / Ioannis Manolaridis / Scott M Jackson / Julia Kowal / Henning Stahlberg / Kaspar P Locher / Abstract: ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs ...ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of human ABCG2 determined by cryo-electron microscopy, providing the first high-resolution insight into a human multidrug transporter. We visualize ABCG2 in complex with two antigen-binding fragments of the human-specific, inhibitory antibody 5D3 that recognizes extracellular loops of the transporter. We observe two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between the transmembrane domains. Combined with functional in vitro analyses, our results suggest a multidrug recognition and transport mechanism of ABCG2, rationalize disease-causing single nucleotide polymorphisms and the allosteric inhibition by the 5D3 antibody, and provide the structural basis of cholesterol recognition by other G-subfamily ABC transporters. | |||||||||
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 | 5njg.cif.gz | 201.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5njg.ent.gz | 153.8 KB | Display | PDB format |
PDBx/mmJSON format | 5njg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nj/5njg ftp://data.pdbj.org/pub/pdb/validation_reports/nj/5njg | HTTPS FTP |
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-Related structure data
Related structure data | 3654MC 5nivC 5nj3C 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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1 |
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-Components
#1: Protein | Mass: 73395.742 Da / Num. of mol.: 2 / Mutation: Has an N-terminal Flag-tag Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABCG2, ABCP, BCRP, BCRP1, MXR / Cell line (production host): HEK293-EBNA / Production host: Homo sapiens (human) / References: UniProt: Q9UNQ0 #2: Antibody | Mass: 23843.633 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): Hybridoma / Production host: Mus musculus (house mouse) #3: Antibody | Mass: 23594.016 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): Hybridoma / Production host: Mus musculus (house mouse) #4: Polysaccharide | Source method: isolated from a genetically manipulated source |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE |
-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 FIELDBright-field microscopy |
Image recording | Electron dose: 67 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum LS |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.78 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 97612 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL |