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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-8652 | |||||||||
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Title | Cryo-EM structure of the human ether-a-go-go related K+ channel | |||||||||
![]() | human ether-a-go-go related K+ channel | |||||||||
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![]() | K+ channel / PAS / CNBHD / voltage sensor / selectivity filter / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() inward rectifier potassium channel complex / negative regulation of potassium ion export across plasma membrane / regulation of heart rate by hormone / Phase 3 - rapid repolarisation / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during action potential / negative regulation of potassium ion transmembrane transport / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane ...inward rectifier potassium channel complex / negative regulation of potassium ion export across plasma membrane / regulation of heart rate by hormone / Phase 3 - rapid repolarisation / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during action potential / negative regulation of potassium ion transmembrane transport / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / C3HC4-type RING finger domain binding / regulation of membrane repolarization / membrane repolarization / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / inward rectifier potassium channel activity / potassium ion homeostasis / membrane depolarization during action potential / ventricular cardiac muscle cell action potential / regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of heart rate by cardiac conduction / voltage-gated potassium channel activity / potassium ion import across plasma membrane / cardiac muscle contraction / voltage-gated potassium channel complex / potassium ion transmembrane transport / regulation of membrane potential / cellular response to xenobiotic stimulus / scaffold protein binding / transcription cis-regulatory region binding / ubiquitin protein ligase binding / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
![]() | Wang WW / MacKinnon R | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM Structure of the Open Human Ether-à-go-go-Related K Channel hERG. Authors: Weiwei Wang / Roderick MacKinnon / ![]() Abstract: The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or ...The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs. A subtle structural feature of the hERG selectivity filter might correlate with its fast inactivation rate, which is key to hERG's role in cardiac action potential repolarization. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 57 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.9 KB 16.9 KB | Display Display | ![]() |
Images | ![]() | 186.6 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5va3MC ![]() 8650C ![]() 8651C ![]() 5va1C ![]() 5va2C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | human ether-a-go-go related K+ channel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X: 0.56563 Å / Y: 0.56563 Å / Z: 0.46445 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : human ether-a-go-go related K+ channel hERG
Entire | Name: human ether-a-go-go related K+ channel hERG |
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Components |
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-Supramolecule #1: human ether-a-go-go related K+ channel hERG
Supramolecule | Name: human ether-a-go-go related K+ channel hERG / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all Details: Truncated hERG construct hERGTs (amino acid residues 141-380 and 871-1005 deleted) with S631A mutation |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Potassium voltage-gated channel subfamily H member 2
Macromolecule | Name: Potassium voltage-gated channel subfamily H member 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 88.885664 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM QRPCTCDFLH GPRTQRRAAA QIAQALLGA EERKVEIAFY RKDGSCFLCL VDVVPVKNED GAVIMFILNF EVVMEKDMVG SGADVLPEYK LQAPRIHRWT I LHYSPFKA ...String: MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM QRPCTCDFLH GPRTQRRAAA QIAQALLGA EERKVEIAFY RKDGSCFLCL VDVVPVKNED GAVIMFILNF EVVMEKDMVG SGADVLPEYK LQAPRIHRWT I LHYSPFKA VWDWLILLLV IYTAVFTPYS AAFLLKETEE GPPATECGYA CQPLAVVDLI VDIMFIVDIL INFRTTYVNA NE EVVSHPG RIAVHYFKGW FLIDMVAAIP FDLLIFGSGS EELIGLLKTA RLLRLVRVAR KLDRYSEYGA AVLFLLMCTF ALI AHWLAC IWYAIGNMEQ PHMDSRIGWL HNLGDQIGKP YNSSGLGGPS IKDKYVTALY FTFSSLTSVG FGNVAPNTNS EKIF SICVM LIGSLMYASI FGNVSAIIQR LYSGTARYHT QMLRVREFIR FHQIPNPLRQ RLEEYFQHAW SYTNGIDMNA VLKGF PECL QADICLHLNR SLLQHCKPFR GATKGCLRAL AMKFKTTHAP PGDTLVHAGD LLTALYFISR GSIEILRGDV VVAILG KND IFGEPLNLYA RPGKSNGDVR ALTYCDLHKI HRDDLLEVLD MYPEFSDHFW SSLEITFNLR DTNMIPGGRQ YQELPRC PA PTPSLLNIPL SSPGRRPRGD VESRLDALQR QLNRLETRLS ADMATVLQLL QRQMTLVPPA YSAVTTPGPG PTSTSPLL P VSPLPTLTLD SLSQVSQFMA CEELPPGAPE LPQEGPTRRL SLPGQLGALT SQPLHRHGSD PGSEASNSLE VLFQ UniProtKB: Potassium voltage-gated channel subfamily H member 2, Potassium voltage-gated channel subfamily H member 2, Potassium voltage-gated channel subfamily H member 2 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 6 mg/mL | ||||||||||||||||||||||||
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Buffer | pH: 7.4 Component:
Details: pH 7.4, adjusted with NaOH | ||||||||||||||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 12 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 101.325 kPa | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 98 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV / Details: one blot: 3 second blot time, 0 blot force. | ||||||||||||||||||||||||
Details | A 1 mL peak fraction was collected and concentrated ~3x to obtain the final ~6 mg/mL sample. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 7420 pixel / Digitization - Dimensions - Height: 7676 pixel / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 1505 / Average exposure time: 15.0 sec. / Average electron dose: 85.0 e/Å2 Details: 50 0.3-second frames were collected for each movie at a dose rate of ~1.8 e-/A2/frame |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 38461 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: AB INITIO MODEL / Overall B value: 180 / Target criteria: Fourier Shell Correlation |
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Output model | ![]() PDB-5va3: |