[English] 日本語
Yorodumi
- PDB-9g9x: Structure of the human two pore domain potassium ion channel TASK... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9g9x
TitleStructure of the human two pore domain potassium ion channel TASK-1 (K2P3.1)
ComponentsPotassium channel subfamily K member 3
KeywordsMEMBRANE PROTEIN / K2P / potassium channel / ion channel
Function / homology
Function and homology information


detection of hypoxic conditions in blood by carotid body chemoreceptor signaling / open rectifier potassium channel activity / regulation of action potential firing rate / TWIK-releated acid-sensitive K+ channel (TASK) / Phase 4 - resting membrane potential / potassium ion leak channel activity / regulation of resting membrane potential / cellular response to acidic pH / outward rectifier potassium channel activity / S100 protein binding ...detection of hypoxic conditions in blood by carotid body chemoreceptor signaling / open rectifier potassium channel activity / regulation of action potential firing rate / TWIK-releated acid-sensitive K+ channel (TASK) / Phase 4 - resting membrane potential / potassium ion leak channel activity / regulation of resting membrane potential / cellular response to acidic pH / outward rectifier potassium channel activity / S100 protein binding / cellular response to zinc ion / negative regulation of cytosolic calcium ion concentration / cochlea development / sodium channel activity / monoatomic ion channel activity / potassium channel activity / potassium ion transmembrane transport / potassium ion transport / monoatomic ion transmembrane transport / chemical synaptic transmission / cellular response to hypoxia / protein heterodimerization activity / response to xenobiotic stimulus / synapse / metal ion binding / plasma membrane
Similarity search - Function
Potassium channel subfamily K member 3 / Two pore domain potassium channel, TASK family / Two pore domain potassium channel / Potassium channel domain / Ion channel
Similarity search - Domain/homology
: / CHOLESTEROL HEMISUCCINATE / Potassium channel subfamily K member 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.13 Å
AuthorsRodstrom, K.E.J. / Hall, P.H. / Tucker, S.J.
Funding support United Kingdom, 3items
OrganizationGrant numberCountry
Biotechnology and Biological Sciences Research Council (BBSRC)BB/T002018/1 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/S008608/1 United Kingdom
Medical Research Council (MRC, United Kingdom)MR/W017741/1 United Kingdom
CitationJournal: Structure / Year: 2025
Title: Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease.
Authors: Peter Rory Hall / Thibault Jouen-Tachoire / Marcus Schewe / Peter Proks / Thomas Baukrowitz / Elisabeth P Carpenter / Simon Newstead / Karin E J Rödström / Stephen J Tucker /
Abstract: TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and ...TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders. A previous crystal structure of TASK-1 revealed a lower "X-gate" as a hotspot for missense gain-of-function (GoF) mutations associated with DDSA (developmental delay with sleep apnea). However, the mechanisms of gating in TASK channels are still not fully understood. Here, we resolve structures for both human TASK-1 and TASK-3 by cryoelectron microscopy (cryo-EM), as well as a recurrent TASK-3 variant (G236R) associated with KCNK9 imprinting syndrome (KIS) (formerly known as Birk-Barel syndrome). Combined with functional studies of the X-gating mechanism, we provide evidence for how a highly conserved gating mechanism becomes defective in disease, and also provide further insight into the pathway of conformational changes that underlie the pH-dependent inhibition of TASK channel activity.
History
DepositionJul 25, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 18, 2024Provider: repository / Type: Initial release
Revision 1.1Jan 15, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.year / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Potassium channel subfamily K member 3
B: Potassium channel subfamily K member 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)62,2989
Polymers60,2342
Non-polymers2,0647
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Potassium channel subfamily K member 3 / Acid-sensitive potassium channel protein TASK-1 / TWIK-related acid-sensitive K(+) channel 1 / Two ...Acid-sensitive potassium channel protein TASK-1 / TWIK-related acid-sensitive K(+) channel 1 / Two pore potassium channel KT3.1 / Two pore K(+) channel KT3.1


Mass: 30117.014 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: K2P3.1 residues M1 to E259 with a TEV protease site. Fused purification tags were cleaved prior to EM sample preparation.
Source: (gene. exp.) Homo sapiens (human) / Gene: KCNK3, TASK, TASK1 / Plasmid: pFB-CT10HF-LIC / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O14649
#2: Chemical
ChemComp-Y01 / CHOLESTEROL HEMISUCCINATE


Mass: 486.726 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C31H50O4
#3: Chemical ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: K
Has ligand of interestN
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: K2P3.1 homodimer / Type: COMPLEX
Details: Protein generated by removal of the 10xHis and FLAG purification tags with TEV protease cleavage
Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.60 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm) / Strain: Sf9
Buffer solutionpH: 7.5
Details: 20 mM HEPES pH 7.5, 200 mM KCl, 0.045% w/v UDM, 0.0045% w/v CHS
SpecimenConc.: 3.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse sample
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: Grid blotted for 3.5 seconds

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1250 nm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 41.17 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 17288
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

EM software
IDNameVersionCategory
1cryoSPARC4.2.1particle selection
2EPUimage acquisition
4cryoSPARC4.2.1.CTF correction
7Coot0.9.8.5model fitting
9cryoSPARC4.4.0initial Euler assignment
10cryoSPARC4.4.1final Euler assignment
12cryoSPARC4.4.13D reconstruction
13PHENIX1.20.1-4487model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.13 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 117627 / Symmetry type: POINT
Atomic model buildingProtocol: FLEXIBLE FIT / Space: REAL
Atomic model buildingPDB-ID: 6RV2

6rv2


Accession code: 6RV2 / Source name: PDB / Type: experimental model

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
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.
  • 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

-
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.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

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