+Open data
-Basic information
Entry | Database: PDB / ID: 7cn0 | ||||||||||||
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Title | Cryo-EM structure of K+-bound hERG channel | ||||||||||||
Components | potassium channel 1 | ||||||||||||
Keywords | TRANSPORT PROTEIN / potassium channel | ||||||||||||
Function / homology | : Function and homology information | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
Authors | Asai, T. / Adachi, N. / Moriya, T. / Kawasaki, M. / Suzuki, K. / Senda, T. / Murata, T. | ||||||||||||
Funding support | Japan, 3items
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Citation | Journal: Structure / Year: 2021 Title: Cryo-EM Structure of K-Bound hERG Channel Complexed with the Blocker Astemizole. Authors: Tatsuki Asai / Naruhiko Adachi / Toshio Moriya / Hideyuki Oki / Takamitsu Maru / Masato Kawasaki / Kano Suzuki / Sisi Chen / Ryohei Ishii / Kazuko Yonemori / Shigeru Igaki / Satoshi Yasuda / ...Authors: Tatsuki Asai / Naruhiko Adachi / Toshio Moriya / Hideyuki Oki / Takamitsu Maru / Masato Kawasaki / Kano Suzuki / Sisi Chen / Ryohei Ishii / Kazuko Yonemori / Shigeru Igaki / Satoshi Yasuda / Satoshi Ogasawara / Toshiya Senda / Takeshi Murata / Abstract: The hERG channel is a voltage-gated potassium channel involved in cardiac repolarization. Off-target hERG inhibition by drugs has become a critical issue in the pharmaceutical industry. The three- ...The hERG channel is a voltage-gated potassium channel involved in cardiac repolarization. Off-target hERG inhibition by drugs has become a critical issue in the pharmaceutical industry. The three-dimensional structure of the hERG channel was recently reported at 3.8-Å resolution using cryogenic electron microscopy (cryo-EM). However, the drug inhibition mechanism remains unclear because of the scarce structural information regarding the drug- and potassium-bound hERG channels. In this study, we obtained the cryo-EM density map of potassium-bound hERG channel complexed with astemizole, a well-known hERG inhibitor that increases risk of potentially fatal arrhythmia, at 3.5-Å resolution. The structure suggested that astemizole inhibits potassium conduction by binding directly below the selectivity filter. Furthermore, we propose a possible binding model of astemizole to the hERG channel and provide insights into the unusual sensitivity of hERG to several drugs. | ||||||||||||
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 | 7cn0.cif.gz | 201.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7cn0.ent.gz | 132.6 KB | Display | PDB format |
PDBx/mmJSON format | 7cn0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7cn0_validation.pdf.gz | 947.1 KB | Display | wwPDB validaton report |
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Full document | 7cn0_full_validation.pdf.gz | 964.3 KB | Display | |
Data in XML | 7cn0_validation.xml.gz | 37.7 KB | Display | |
Data in CIF | 7cn0_validation.cif.gz | 49.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cn/7cn0 ftp://data.pdbj.org/pub/pdb/validation_reports/cn/7cn0 | HTTPS FTP |
-Related structure data
Related structure data | 30412MC 7cn1C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10628 (Title: Cryo-EM structure of K+-bound hERG channel / Data size: 1.4 TB Data #1: Cryo-EM structure of K+-bound hERG channel [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 91792.086 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: BacMam expression vector / Production host: Homo sapiens (human) / Strain (production host): Expi293F cells #2: Chemical | Has ligand of interest | Y | |
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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
Component | Name: potassium channel / Type: ORGANELLE OR CELLULAR COMPONENT / Details: homo-tetramer / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Expi293F cells / Plasmid: BacMam expression vector |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was mono-disperse. |
Specimen support | Details: The grid was washed by acetone prior to use. / 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: 291 K / Details: Blotting time was 5 seconds (blot force 10) |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 120000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 56.13 sec. / Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1496 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 999720 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 173770 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |