+Open data
-Basic information
Entry | Database: PDB / ID: 7pxg | ||||||
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Title | Verruculogen-bound Drosophila Slo channel | ||||||
Components | Isoform J of Calcium-activated potassium channel slowpoke | ||||||
Keywords | TRANSPORT PROTEIN / Potassium transport / BK channel | ||||||
Function / homology | Function and homology information Sperm Motility And Taxes / negative regulation of neuromuscular synaptic transmission / male courtship behavior, veined wing generated song production / regulation of synaptic assembly at neuromuscular junction / large conductance calcium-activated potassium channel activity / calcium-activated potassium channel activity / circadian behavior / monoatomic ion channel complex / potassium ion transmembrane transport / potassium ion transport ...Sperm Motility And Taxes / negative regulation of neuromuscular synaptic transmission / male courtship behavior, veined wing generated song production / regulation of synaptic assembly at neuromuscular junction / large conductance calcium-activated potassium channel activity / calcium-activated potassium channel activity / circadian behavior / monoatomic ion channel complex / potassium ion transmembrane transport / potassium ion transport / circadian rhythm / postsynaptic membrane / neuron projection / response to xenobiotic stimulus / neuronal cell body / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Drosophila melanogaster (fruit fly) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.73 Å | ||||||
Authors | Raisch, T. / Brockmann, A. / Ebbinghaus-Kintscher, U. / Freigang, J. / Gutbrod, O. / Kubicek, J. / Maertens, B. / Hofnagel, O. / Raunser, S. | ||||||
Funding support | Germany, 1items
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Citation | Journal: Nat Commun / Year: 2021 Title: Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM. Authors: Tobias Raisch / Andreas Brockmann / Ulrich Ebbinghaus-Kintscher / Jörg Freigang / Oliver Gutbrod / Jan Kubicek / Barbara Maertens / Oliver Hofnagel / Stefan Raunser / Abstract: Slowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca concentrations and are ...Slowpoke (Slo) potassium channels display extraordinarily high conductance, are synergistically activated by a positive transmembrane potential and high intracellular Ca concentrations and are important targets for insecticides and antiparasitic drugs. However, it is unknown how these compounds modulate ion translocation and whether there are insect-specific binding pockets. Here, we report structures of Drosophila Slo in the Ca-bound and Ca-free form and in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside. Whereas the architecture and gating mechanism of Slo channels are conserved, potential insect-specific binding pockets exist. Verruculogen inhibits K transport by blocking the Ca-induced activation signal and precludes K from entering the selectivity filter. Emodepside decreases the conductance by suboptimal K coordination and uncouples ion gating from Ca and voltage sensing. Our results expand the mechanistic understanding of Slo regulation and lay the foundation for the rational design of regulators of Slo and other voltage-gated ion channels. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7pxg.cif.gz | 648.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7pxg.ent.gz | 521.9 KB | Display | PDB format |
PDBx/mmJSON format | 7pxg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7pxg_validation.pdf.gz | 2.1 MB | Display | wwPDB validaton report |
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Full document | 7pxg_full_validation.pdf.gz | 2.1 MB | Display | |
Data in XML | 7pxg_validation.xml.gz | 110.5 KB | Display | |
Data in CIF | 7pxg_validation.cif.gz | 161.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/px/7pxg ftp://data.pdbj.org/pub/pdb/validation_reports/px/7pxg | HTTPS FTP |
-Related structure data
Related structure data | 13702MC 7pxeC 7pxfC 7pxhC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 130919.094 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Drosophila melanogaster (fruit fly) / Gene: slo, CG10693 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q03720 |
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-Non-polymers , 6 types, 32 molecules
#2: Chemical | ChemComp-8H5 / #3: Chemical | ChemComp-CA / #4: Chemical | ChemComp-MG / #5: Chemical | ChemComp-6PL / ( #6: Chemical | ChemComp-CLR / #7: Chemical | ChemComp-K / |
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-Details
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: Slo tetramer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Drosophila melanogaster (fruit fly) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.7 |
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: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 80.4 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19_4085: / Classification: refinement | ||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1131410 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.73 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 66077 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5TJ6 Accession code: 5TJ6 / Source name: PDB / Type: experimental model |