+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30445 | |||||||||
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Title | human KCNQ2 in complex with retigabine | |||||||||
Map data | ||||||||||
Sample |
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Keywords | ion channel / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information axon initial segment / node of Ranvier / Voltage gated Potassium channels / voltage-gated monoatomic cation channel activity / Interaction between L1 and Ankyrins / ankyrin binding / action potential / voltage-gated potassium channel activity / voltage-gated potassium channel complex / potassium ion transmembrane transport ...axon initial segment / node of Ranvier / Voltage gated Potassium channels / voltage-gated monoatomic cation channel activity / Interaction between L1 and Ankyrins / ankyrin binding / action potential / voltage-gated potassium channel activity / voltage-gated potassium channel complex / potassium ion transmembrane transport / nervous system development / chemical synaptic transmission / calmodulin binding / synapse / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Li X / Lv D | |||||||||
Funding support | China, 2 items
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Citation | Journal: 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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30445.map.gz | 43.4 MB | EMDB map data format | |
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Header (meta data) | emd-30445-v30.xml emd-30445.xml | 10 KB 10 KB | Display Display | EMDB header |
Images | emd_30445.png | 125.9 KB | ||
Filedesc metadata | emd-30445.cif.gz | 5.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30445 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30445 | HTTPS FTP |
-Validation report
Summary document | emd_30445_validation.pdf.gz | 520.5 KB | Display | EMDB validaton report |
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Full document | emd_30445_full_validation.pdf.gz | 520.1 KB | Display | |
Data in XML | emd_30445_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_30445_validation.cif.gz | 6.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30445 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30445 | HTTPS FTP |
-Related structure data
Related structure data | 7cr2MC 7cr0C 7cr1C 7cr3C 7cr4C 7cr7C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30445.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : voltage-gated potassium channel KCNQ2
Entire | Name: voltage-gated potassium channel KCNQ2 |
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Components |
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-Supramolecule #1: voltage-gated potassium channel KCNQ2
Supramolecule | Name: voltage-gated potassium channel KCNQ2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Potassium voltage-gated channel subfamily KQT member 2
Macromolecule | Name: Potassium voltage-gated channel subfamily KQT member 2 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 73.627812 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAGKPPKRNA FYRKLQNFLY NVLERPRGWA FIYHAYVFLL VFSCLVLSVF STIKEYEKSS EGALYILEIV TIVVFGVEYF VRIWAAGCC CRYRGWRGRL KFARKPFCVI DIMVLIASIA VLAAGSQGNV FATSALRSLR FLQILRMIRM DRRGGTWKLL G SVVYAHSK ...String: MAGKPPKRNA FYRKLQNFLY NVLERPRGWA FIYHAYVFLL VFSCLVLSVF STIKEYEKSS EGALYILEIV TIVVFGVEYF VRIWAAGCC CRYRGWRGRL KFARKPFCVI DIMVLIASIA VLAAGSQGNV FATSALRSLR FLQILRMIRM DRRGGTWKLL G SVVYAHSK ELVTAWYIGF LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI GV SFFALPA GILGSGFALK VQEQHRQKHF EKRRNPAAGL IQSAWRFYAT NLSRTDLHST WQYYERTVTV PMYSSQTQTY GAS RLIPPL NQLELLRNLK SKSGLAFRKD PPPEPSPSKG SPCRGPLCGC CPGRSSQKVS LKDRVFSSPR GVAAKGKGSP QAQT VRRSP SADQSLEDSP SKVPKSWSFG DRSRARQAFR IKGAASRQNS EEASLPGEDI VDDKSCPCEF VTEDLTPGLK VSIRA VCVM RFLVSKRKFK ESLRPYDVMD VIEQYSAGHL DMLSRIKSLQ SRVDQIVGRG PAITDKDRTK GPAEAELPED PSMMGR LGK VEKQVLSMEK KLDFLVNIYM QRMGIPPTET EAYFGAKEPE PAPPYHSPED SREHVDRHGC IVKIVRSSSS TGQKNFS VE GGSSGGWSHP QFEK UniProtKB: Potassium voltage-gated channel subfamily KQT member 2 |
-Macromolecule #2: ethyl N-[2-azanyl-4-[(4-fluorophenyl)methylamino]phenyl]carbamate
Macromolecule | Name: ethyl N-[2-azanyl-4-[(4-fluorophenyl)methylamino]phenyl]carbamate type: ligand / ID: 2 / Number of copies: 4 / Formula: FBX |
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Molecular weight | Theoretical: 303.331 Da |
Chemical component information | ChemComp-FBX: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.556 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 96910 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: PROJECTION MATCHING |