+Open data
-Basic information
Entry | Database: PDB / ID: 8izy | |||||||||||||||
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Title | Human KCNQ2-CaM in complex with HN37 | |||||||||||||||
Components | Potassium voltage-gated channel subfamily KQT member 2 | |||||||||||||||
Keywords | MEMBRANE PROTEIN / potassium voltage-gated channel / HN37 | |||||||||||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||||||||
Authors | Ma, D. / Li, X. / Guo, J. | |||||||||||||||
Funding support | China, 4items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8izy.cif.gz | 419 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8izy.ent.gz | 340.9 KB | Display | PDB format |
PDBx/mmJSON format | 8izy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8izy_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8izy_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8izy_validation.xml.gz | 39.2 KB | Display | |
Data in CIF | 8izy_validation.cif.gz | 53.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/iz/8izy ftp://data.pdbj.org/pub/pdb/validation_reports/iz/8izy | HTTPS FTP |
-Related structure data
Related structure data | 35877MC 8j00C 8j01C 8j02C 8j03C 8j04C 8j05C 8w4uC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 73627.812 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNQ2 / Production host: Homo sapiens (human) / References: UniProt: O43526 #2: Chemical | ChemComp-9MF / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human KCNQ2-CaM in complex with HN37 / Type: COMPLEX / Entity ID: #1 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1300 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 367290 / Symmetry type: POINT |