[English] 日本語
Yorodumi
- PDB-7cr7: human KCNQ2-CaM in complex with retigabine -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7cr7
Titlehuman KCNQ2-CaM in complex with retigabine
Components
  • Calmodulin-3
  • Potassium voltage-gated channel subfamily KQT member 2
KeywordsTRANSPORT PROTEIN / ion channel
Function / homology
Function and homology information


transporter inhibitor activity / axon initial segment / Voltage gated Potassium channels / establishment of protein localization to mitochondrial membrane / type 3 metabotropic glutamate receptor binding / node of Ranvier / voltage-gated monoatomic cation channel activity / Interaction between L1 and Ankyrins / ankyrin binding / response to corticosterone ...transporter inhibitor activity / axon initial segment / Voltage gated Potassium channels / establishment of protein localization to mitochondrial membrane / type 3 metabotropic glutamate receptor binding / node of Ranvier / voltage-gated monoatomic cation channel activity / Interaction between L1 and Ankyrins / ankyrin binding / response to corticosterone / negative regulation of high voltage-gated calcium channel activity / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / presynaptic endocytosis / nitric-oxide synthase binding / regulation of cell communication by electrical coupling involved in cardiac conduction / regulation of synaptic vesicle exocytosis / calcineurin-mediated signaling / action potential / adenylate cyclase binding / protein phosphatase activator activity / voltage-gated potassium channel activity / catalytic complex / detection of calcium ion / regulation of synaptic vesicle endocytosis / regulation of cardiac muscle contraction / postsynaptic cytosol / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / phosphatidylinositol 3-kinase binding / presynaptic cytosol / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / titin binding / sperm midpiece / regulation of calcium-mediated signaling / voltage-gated potassium channel complex / potassium ion transmembrane transport / calcium channel complex / substantia nigra development / regulation of heart rate / calyx of Held / response to amphetamine / adenylate cyclase activator activity / sarcomere / protein serine/threonine kinase activator activity / nitric-oxide synthase regulator activity / regulation of cytokinesis / spindle microtubule / calcium channel regulator activity / response to calcium ion / mitochondrial membrane / G2/M transition of mitotic cell cycle / Schaffer collateral - CA1 synapse / long-term synaptic potentiation / spindle pole / calcium-dependent protein binding / synaptic vesicle membrane / nervous system development / myelin sheath / growth cone / chemical synaptic transmission / vesicle / transmembrane transporter binding / calmodulin binding / G protein-coupled receptor signaling pathway / protein domain specific binding / calcium ion binding / synapse / centrosome / protein kinase binding / protein-containing complex / nucleus / membrane / plasma membrane / cytoplasm
Similarity search - Function
Potassium channel, voltage dependent, KCNQ2 / Ankyrin-G binding site / Ankyrin-G binding motif of KCNQ2-3 / Unstructured region on Potassium channel subunit alpha KvLQT2 / Potassium channel, voltage dependent, KCNQ / Potassium channel, voltage dependent, KCNQ, C-terminal / KCNQ voltage-gated potassium channel / EF-hand / : / Recoverin; domain 1 ...Potassium channel, voltage dependent, KCNQ2 / Ankyrin-G binding site / Ankyrin-G binding motif of KCNQ2-3 / Unstructured region on Potassium channel subunit alpha KvLQT2 / Potassium channel, voltage dependent, KCNQ / Potassium channel, voltage dependent, KCNQ, C-terminal / KCNQ voltage-gated potassium channel / EF-hand / : / Recoverin; domain 1 / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-FBX / Potassium voltage-gated channel subfamily KQT member 2 / Calmodulin-3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsLi, X. / Lv, D. / Wang, J. / Ye, S. / Guo, J.
Funding support China, 2items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2018YFA0508100 China
National Natural Science Foundation of China (NSFC)31870724 China
CitationJournal: Cell Res / Year: 2021
Title: Molecular basis for ligand activation of the human KCNQ2 channel.
Authors: Xiaoxiao Li / Qiansen Zhang / Peipei Guo / Jie Fu / Lianghe Mei / Dashuai Lv / Jiangqin Wang / Dongwu Lai / Sheng Ye / Huaiyu Yang / Jiangtao Guo /
Abstract: The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper- ...The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design.
History
DepositionAug 12, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 16, 2020Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Sep 16, 2020Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Nov 11, 2020Group: Structure summary / Category: chem_comp / Item: _chem_comp.pdbx_synonyms
Revision 1.2Jan 13, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year
Revision 1.3Mar 27, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Jun 25, 2025Group: Data collection / Structure summary / Category: em_admin / em_software / pdbx_entry_details
Item: _em_admin.last_update / _em_software.name / _pdbx_entry_details.has_protein_modification
Revision 1.1Jun 25, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-30448
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Potassium voltage-gated channel subfamily KQT member 2
F: Calmodulin-3
B: Potassium voltage-gated channel subfamily KQT member 2
C: Calmodulin-3
D: Potassium voltage-gated channel subfamily KQT member 2
E: Calmodulin-3
G: Potassium voltage-gated channel subfamily KQT member 2
H: Calmodulin-3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)363,13512
Polymers361,9218
Non-polymers1,2134
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area34490 Å2
ΔGint-308 kcal/mol
Surface area102070 Å2

-
Components

#1: Protein
Potassium voltage-gated channel subfamily KQT member 2 / KQT-like 2 / Neuroblastoma-specific potassium channel subunit alpha KvLQT2 / Voltage-gated ...KQT-like 2 / Neuroblastoma-specific potassium channel subunit alpha KvLQT2 / Voltage-gated potassium channel subunit Kv7.2


Mass: 73627.812 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KCNQ2 / Cell line (production host): HEK297 / Production host: Homo sapiens (human) / References: UniProt: O43526
#2: Protein
Calmodulin-3


Mass: 16852.545 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P0DP25
#3: Chemical
ChemComp-FBX / ethyl N-[2-azanyl-4-[(4-fluorophenyl)methylamino]phenyl]carbamate / Retigabine, Ezogabine


Mass: 303.331 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C16H18FN3O2 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1voltage-gated potassium channel KCNQ2COMPLEX#1-#20RECOMBINANT
2Potassium voltage-gated channel subfamily KQT member 2COMPLEX#11RECOMBINANT
3Calmodulin-3COMPLEX#21RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Homo sapiens (human)9606
33Homo sapiens (human)9606
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
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
Image recordingElectron dose: 1.556 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.15.2_3472: / Classification: refinement
EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 67671 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00516548
ELECTRON MICROSCOPYf_angle_d0.74522372
ELECTRON MICROSCOPYf_dihedral_angle_d8.9789688
ELECTRON MICROSCOPYf_chiral_restr0.0412428
ELECTRON MICROSCOPYf_plane_restr0.0052816

+
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