[English] 日本語
Yorodumi
- PDB-5va2: Cryo-EM structure of the human ether-a-go-go related K+ channel -

+
Open data


ID or keywords:

Loading...

no data

-
Basic information

Entry
Database: PDB / ID: 5va2
TitleCryo-EM structure of the human ether-a-go-go related K+ channel
ComponentsPotassium voltage-gated channel subfamily H member 2
KeywordsTRANSPORT PROTEIN / K+ channel / PAS / CNBHD / voltage sensor / selectivity filter
Function / homologyCyclic nucleotide-binding domain / Ion transport protein / PAS-associated, C-terminal / PAC motif / PAS domain / Potassium channel, voltage-dependent, EAG/ELK/ERG / Potassium channel, voltage-dependent, ERG / PAS domain / cAMP/cGMP binding motif profile. / PAS repeat profile. ...Cyclic nucleotide-binding domain / Ion transport protein / PAS-associated, C-terminal / PAC motif / PAS domain / Potassium channel, voltage-dependent, EAG/ELK/ERG / Potassium channel, voltage-dependent, ERG / PAS domain / cAMP/cGMP binding motif profile. / PAS repeat profile. / Ion transport domain / RmlC-like jelly roll fold / PAC domain profile. / Voltage gated Potassium channels / Cyclic nucleotide-binding-like / Phase 3 - rapid repolarisation / Voltage-dependent channel domain superfamily / PAS domain superfamily / Cyclic nucleotide-binding domain / negative regulation of potassium ion export / inward rectifier potassium channel complex / regulation of heart rate by hormone / potassium ion homeostasis / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / potassium ion export across plasma membrane / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during action potential / potassium ion export / membrane repolarization during cardiac muscle cell action potential / membrane repolarization / negative regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / regulation of membrane repolarization / regulation of ventricular cardiac muscle cell membrane repolarization / membrane depolarization during action potential / inward rectifier potassium channel activity / positive regulation of potassium ion transmembrane transport / ventricular cardiac muscle cell action potential / regulation of heart rate by cardiac conduction / C3HC4-type RING finger domain binding / regulation of potassium ion transmembrane transport / potassium ion transmembrane transport / voltage-gated potassium channel complex / regulation of membrane potential / voltage-gated potassium channel activity / cardiac muscle contraction / phosphorelay sensor kinase activity / cellular response to drug / scaffold protein binding / ubiquitin protein ligase binding / cell surface / perinuclear region of cytoplasm / protein homodimerization activity / identical protein binding / plasma membrane / Potassium voltage-gated channel subfamily H member 2
Function and homology information
Specimen sourceHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 3.8 Å resolution
Model detailstruncation hERGTs
AuthorsWang, W.W. / MacKinnon, R.
CitationJournal: Cell / Year: 2017
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.
Validation Report
SummaryFull reportAbout validation report
DateDeposition: Mar 24, 2017 / Release: May 3, 2017
RevisionDateData content typeGroupCategoryItemProviderType
1.0May 3, 2017Structure modelrepositoryInitial release
1.1Sep 13, 2017Structure modelAuthor supporting evidence / Data collectionem_software / pdbx_audit_support_em_software.name / _pdbx_audit_support.funding_organization

-
Structure visualization

Movie
  • Biological unit as complete point assembly
  • Imaged by Jmol
  • Download
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-8651
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Potassium voltage-gated channel subfamily H member 2


Theoretical massNumber of molelcules
Total (without water)92,2811
Polyers92,2811
Non-polymers00
Water0
1
A: Potassium voltage-gated channel subfamily H member 2

A: Potassium voltage-gated channel subfamily H member 2

A: Potassium voltage-gated channel subfamily H member 2

A: Potassium voltage-gated channel subfamily H member 2


Theoretical massNumber of molelcules
Total (without water)369,1224
Polyers369,1224
Non-polymers00
Water0
TypeNameSymmetry operationNumber
point symmetry operation4
2


  • idetical with deposited unit in distinct coordinate
  • point asymmetric unit
TypeNameSymmetry operationNumber
point symmetry operation1
3


  • idetical with deposited unit in distinct coordinate
  • point asymmetric unit, std point frame
TypeNameSymmetry operationNumber
transform to point frame1

-
Components

#1: Protein/peptide Potassium voltage-gated channel subfamily H member 2 / Eag homolog / Ether-a-go-go-related gene potassium channel 1 / hERG1 / Voltage-gated potassium channel subunit Kv11.1


Mass: 92280.539 Da / Num. of mol.: 1 / Fragment: UNP residues 1-140,381-870,1006-1159 / Source: (gene. exp.) Homo sapiens (human) / Gene: KCNH2, ERG, ERG1, HERG / Plasmid name: BacMam / Cell line (production host): HEK293S GnTI- / Production host: Homo sapiens (human) / References: UniProt: Q12809

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / Reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: human ether-a-go-go related K+ channel hERG / Type: ORGANELLE OR CELLULAR COMPONENT
Details: Truncated hERG construct hERGTs (amino acid residues 141-350 and 871-1005 deleted)
Entity ID: 1 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Cell: HEK293S GnTI- / Organism: Homo sapiens (human) / Plasmid: BacMam
Buffer solutionDetails: pH 7.4, adjusted with NaOH / pH: 7.4
Buffer component
IDConc.NameFormulaBuffer ID
120 mMHEPESC8H18N2O4S1
2300 mMpotassium chlorideKCl1
310 mMDithiothreitolC4H10O2S21
40.025 %n-Dodecyl beta-D-maltosideC24H46O111
50.005 %Cholesteryl hemisuccinateC31H50O41
60.025 mg/mLPOPE:POPC:POPA 5:5:11
70.5 mMtris(2-carboxyethyl)phosphineC9H15O6P1
SpecimenConc.: 6 mg/ml
Details: A 1 mL peak fraction was collected and concentrated ~3x to obtain the final ~6 mg/mL sample.
Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 400 / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 98 % / Chamber temperature: 298 kelvins / Details: one blot: 3 second blot time, 0 blot force

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyMicroscope model: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Calibrated magnification: 38461 / Nominal defocus max: 3500 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 15 sec. / Electron dose: 85 e/Å2
Details: 50 0.3-second frames were collected for each movie at a dose rate of ~1.8 e-/A2/frame
Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number of grids imaged: 1 / Number of real images: 2443
Image scansWidth: 7420 / Height: 7676 / Movie frames/image: 50 / Used frames/image: 1-50

-
Processing

EM software
IDNameVersionCategory
1RELION AUTOPICK1.4particle selection
2SerialEM3.5image acquisition
3DigitalMicrograph3image acquisition
5RELION1.4CTF correction
6CTFFIND4CTF correction
9UCSF Chimera1.10.2model fitting
10Coot0.8.2model fitting
12RELION1.4initial Euler assignment
13FREALIGN9.11final Euler assignment
14RELION1.4classification
15FREALIGN9.113D reconstruction
16REFMAC5.8model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionDetails: ~555000 particles from autopick / Number of particles selected: 555000
3D reconstructionResolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 144 / Algorithm: FOURIER SPACE / Number of class averages: 2 / Symmetry type: POINT
Atomic model buildingOverall b value: 150 / Ref protocol: AB INITIO MODEL / Ref space: RECIPROCAL / Target criteria: Fourier Shell Correlation

+
About Yorodumi

-
News

-
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.

External links: wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

+
Apr 13, 2016. Omokage search got faster

Omokage search got faster

  • The computation time became ~1/2 compared to the previous version by re-optimization of data accession
  • Enjoy "shape similarity" of biomolecules, more!

Related info.: Omokage search

Read more

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.

Related info.: EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more