+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35877 | |||||||||||||||
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Title | Human KCNQ2-CaM in complex with HN37 | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Keywords | potassium voltage-gated channel / HN37 / MEMBRANE 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: 2.5 Å | |||||||||||||||
Authors | Ma D / Li X / Guo J | |||||||||||||||
Funding support | China, 4 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Ligand activation mechanisms of human KCNQ2 channel. Authors: Demin Ma / Yueming Zheng / Xiaoxiao Li / Xiaoyu Zhou / Zhenni Yang / Yan Zhang / Long Wang / Wenbo Zhang / Jiajia Fang / Guohua Zhao / Panpan Hou / Fajun Nan / Wei Yang / Nannan Su / ...Authors: Demin Ma / Yueming Zheng / Xiaoxiao Li / Xiaoyu Zhou / Zhenni Yang / Yan Zhang / Long Wang / Wenbo Zhang / Jiajia Fang / Guohua Zhao / Panpan Hou / Fajun Nan / Wei Yang / Nannan Su / Zhaobing Gao / Jiangtao Guo / Abstract: The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but ...The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35877.map.gz | 49.1 MB | EMDB map data format | |
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Header (meta data) | emd-35877-v30.xml emd-35877.xml | 15.2 KB 15.2 KB | Display Display | EMDB header |
Images | emd_35877.png | 59.9 KB | ||
Filedesc metadata | emd-35877.cif.gz | 5.8 KB | ||
Others | emd_35877_half_map_1.map.gz emd_35877_half_map_2.map.gz | 37 MB 37 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35877 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35877 | HTTPS FTP |
-Validation report
Summary document | emd_35877_validation.pdf.gz | 873.3 KB | Display | EMDB validaton report |
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Full document | emd_35877_full_validation.pdf.gz | 872.8 KB | Display | |
Data in XML | emd_35877_validation.xml.gz | 11.7 KB | Display | |
Data in CIF | emd_35877_validation.cif.gz | 13.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35877 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35877 | HTTPS FTP |
-Related structure data
Related structure data | 8izyMC 8j00C 8j01C 8j02C 8j03C 8j04C 8j05C 8w4uC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_35877.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:
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-Supplemental data
-Half map: #2
File | emd_35877_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35877_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : human KCNQ2-CaM in complex with HN37
Entire | Name: human KCNQ2-CaM in complex with HN37 |
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Components |
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-Supramolecule #1: human KCNQ2-CaM in complex with HN37
Supramolecule | Name: human KCNQ2-CaM in complex with HN37 / 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: methyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynyl-amino]-2,6-dimeth...
Macromolecule | Name: methyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynyl-amino]-2,6-dimethyl-phenyl]carbamate type: ligand / ID: 2 / Number of copies: 8 / Formula: 9MF |
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Molecular weight | Theoretical: 340.391 Da |
Chemical component information | ChemComp-9MF: |
-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: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.3 µm / Nominal defocus min: 1.1 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 367290 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |