[English] 日本語
Yorodumi
- EMDB-38522: Human KCNQ2-CaM in complex with QO-83 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-38522
TitleHuman KCNQ2-CaM in complex with QO-83
Map data
Sample
  • Complex: human KCNQ2-CaM in complex with QO-83
    • Protein or peptide: Potassium voltage-gated channel subfamily KQT member 2
    • Protein or peptide: Calmodulin-1
  • Ligand: ~{N}-[2-azanyl-3-fluoranyl-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]-3-cyclopentyl-propanamide
KeywordsKCNQ2 / human voltage-gated potassium channel / MEMBRANE PROTEIN
Function / homology
Function and homology information


axon initial segment / Voltage gated Potassium channels / node of Ranvier / Interaction between L1 and Ankyrins / CaM pathway / ankyrin binding / Cam-PDE 1 activation / voltage-gated monoatomic cation channel activity / Sodium/Calcium exchangers / Calmodulin induced events ...axon initial segment / Voltage gated Potassium channels / node of Ranvier / Interaction between L1 and Ankyrins / CaM pathway / ankyrin binding / Cam-PDE 1 activation / voltage-gated monoatomic cation channel activity / Sodium/Calcium exchangers / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of high voltage-gated calcium channel activity / PKA activation / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / negative regulation of ryanodine-sensitive calcium-release channel activity / organelle localization by membrane tethering / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / presynaptic endocytosis / regulation of cell communication by electrical coupling involved in cardiac conduction / Synthesis of IP3 and IP4 in the cytosol / Phase 0 - rapid depolarisation / calcineurin-mediated signaling / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / RHO GTPases activate PAKs / regulation of ryanodine-sensitive calcium-release channel activity / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / Long-term potentiation / protein phosphatase activator activity / action potential / Calcineurin activates NFAT / voltage-gated potassium channel activity / Regulation of MECP2 expression and activity / DARPP-32 events / Smooth Muscle Contraction / detection of calcium ion / regulation of cardiac muscle contraction / catalytic complex / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / calcium channel inhibitor activity / Activation of AMPK downstream of NMDARs / presynaptic cytosol / cellular response to interferon-beta / Protein methylation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / titin binding / Ion homeostasis / eNOS activation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / regulation of calcium-mediated signaling / voltage-gated potassium channel complex / potassium ion transmembrane transport / FCERI mediated Ca+2 mobilization / calcium channel complex / substantia nigra development / regulation of heart rate / FCGR3A-mediated IL10 synthesis / Ras activation upon Ca2+ influx through NMDA receptor / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / calyx of Held / adenylate cyclase activator activity / sarcomere / protein serine/threonine kinase activator activity / VEGFR2 mediated cell proliferation / regulation of cytokinesis / VEGFR2 mediated vascular permeability / spindle microtubule / positive regulation of receptor signaling pathway via JAK-STAT / Translocation of SLC2A4 (GLUT4) to the plasma membrane / calcium channel regulator activity / RAF activation / Transcriptional activation of mitochondrial biogenesis / response to calcium ion / cellular response to type II interferon / G2/M transition of mitotic cell cycle / Stimuli-sensing channels / spindle pole / Signaling by RAF1 mutants / calcium-dependent protein binding / RAS processing / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / Signaling by BRAF and RAF1 fusions / long-term synaptic potentiation / Platelet degranulation / sperm midpiece / nervous system development
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 domain pair / EF-hand, calcium binding motif ...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 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
Similarity search - Domain/homology
Potassium voltage-gated channel subfamily KQT member 2 / Calmodulin-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsZhao YW / Yang ZN / Guo JT / Du XN
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)U21A20359 China
CitationJournal: Cell Rep / Year: 2026
Title: Structure basis for the activation of KCNQ2 by endogenous and exogenous ligands.
Authors: Yiwen Zhao / Zhenni Yang / Sai Shi / Han Hao / Xinmeng Li / Demin Ma / Nannan Su / Weixin Zhao / Jicheng Shao / Yating An / Ke Wang / Yinuo Liu / Lu Zou / Jinlong Qi / Hailin Zhang / Jiangtao Guo / Xiaona Du /
Abstract: The voltage-gated potassium channel KCNQ2 is crucial for stabilizing neuronal membrane potential, and its mutations can cause various epilepsies. KCNQ2 is activated by endogenous ligand ...The voltage-gated potassium channel KCNQ2 is crucial for stabilizing neuronal membrane potential, and its mutations can cause various epilepsies. KCNQ2 is activated by endogenous ligand phosphatidylinositol-4,5-bisphosphate (PIP) and exogenous ligands, yet the structural mechanisms underlying these activations remain unclear. Here, we report the cryo-electron microscopy structures of human KCNQ2 in complex with exogenous ligands QO-58 and QO-83 in the absence or presence of PIP in either closed or open conformation. While QO-83 binds in the classical fenestration pocket of the pore domain, QO-58 mainly binds at the flank of S4 in the voltage-sensing domain. These structures, along with electrophysiological assays and computational studies, provide mechanistic insights into the ligand activation of KCNQ2 and may guide the development of anti-epileptic drugs targeting KCNQ2.
History
DepositionDec 31, 2023-
Header (metadata) releaseJan 1, 2025-
Map releaseJan 1, 2025-
UpdateJan 21, 2026-
Current statusJan 21, 2026Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_38522.png

Downloads & links

-
Map

FileDownload / File: emd_38522.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 240 pix.
= 223.2 Å		0.93 Å/pix.
x 240 pix.
= 223.2 Å		0.93 Å/pix.
x 240 pix.
= 223.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.93 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.00743
Minimum - Maximum-0.013979437 - 0.03480876
Average (Standard dev.)0.00025930224 (±0.0017858751)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 223.2 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_38522_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_38522_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human KCNQ2-CaM in complex with QO-83

EntireName: human KCNQ2-CaM in complex with QO-83
Components
  • Complex: human KCNQ2-CaM in complex with QO-83
    • Protein or peptide: Potassium voltage-gated channel subfamily KQT member 2
    • Protein or peptide: Calmodulin-1
  • Ligand: ~{N}-[2-azanyl-3-fluoranyl-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]-3-cyclopentyl-propanamide

-
Supramolecule #1: human KCNQ2-CaM in complex with QO-83

SupramoleculeName: human KCNQ2-CaM in complex with QO-83 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Potassium voltage-gated channel subfamily KQT member 2

MacromoleculeName: Potassium voltage-gated channel subfamily KQT member 2
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 95.976742 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG GAGAGKPPKR NAFYRKLQNF LYNVLERPR GWAFIYHAYV FLLVFSCLVL SVFSTIKEYE KSSEGALYIL EIVTIVVFGV EYFVRIWAAG CCCRYRGWRG R LKFARKPF ...String:
MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG GAGAGKPPKR NAFYRKLQNF LYNVLERPR GWAFIYHAYV FLLVFSCLVL SVFSTIKEYE KSSEGALYIL EIVTIVVFGV EYFVRIWAAG CCCRYRGWRG R LKFARKPF CVIDIMVLIA SIAVLAAGSQ GNVFATSALR SLRFLQILRM IRMDRRGGTW KLLGSVVYAH SKELVTAWYI GF LCLILAS FLVYLAEKGE NDHFDTYADA LWWGLITLTT IGYGDKYPQT WNGRLLAATF TLIGVSFFAL PAGILGSGFA LKV QEQHRQ KHFEKRRNPA AGLIQSAWRF YATNLSRTDL HSTWQYYERT VTVPMYSSQT QTYGASRLIP PLNQLELLRN LKSK SGLAF RKDPPPEPSP SKGSPCRGPL CGCCPGRSSQ KVSLKDRVFS SPRGVAAKGK GSPQAQTVRR SPSADQSLED SPSKV PKSW SFGDRSRARQ AFRIKGAASR QNSEEASLPG EDIVDDKSCP CEFVTEDLTP GLKVSIRAVC VMRFLVSKRK FKESLR PYD VMDVIEQYSA GHLDMLSRIK SLQSRVDQIV GRGPAITDKD RTKGPAEAEL PEDPSMMGRL GKVEKQVLSM EKKLDFL VN IYMQRMGIPP TETEAYFGAK EPEPAPPYHS PEDSREHVDR HGCIVKIVRS SSSTGQKNFS APPAAPPVQC PPSTSWQP Q SHPRQGHGTS PVGDHGSLVR IPPPPAHERS LSAYGGGNRA SMEFLRQEDT PGCRPPEGNL RDSDTSISIP SVDHEELER SFSGFSISQS KENLDALNSC YAAVAPCAKV RPYIAEGESD TDSDLCTPCG PPPRSATGEG PFGDVGWAGP RK

UniProtKB: Potassium voltage-gated channel subfamily KQT member 2

-
Macromolecule #2: Calmodulin-1

MacromoleculeName: Calmodulin-1 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 16.852545 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK

UniProtKB: Calmodulin-1

-
Macromolecule #3: ~{N}-[2-azanyl-3-fluoranyl-4-[[4-(trifluoromethyl)phenyl]methylam...

MacromoleculeName: ~{N}-[2-azanyl-3-fluoranyl-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]-3-cyclopentyl-propanamide
type: ligand / ID: 3 / Number of copies: 4 / Formula: A1LWZ
Molecular weightTheoretical: 423.447 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 52.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7cr3

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 73879
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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