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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-13703 | |||||||||
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Title | Emodepside-bound Drosophila Slo channel | |||||||||
![]() | Sharpened by Phenix.Autosharpen | |||||||||
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Function / homology | ![]() Sperm Motility And Taxes / negative regulation of neuromuscular synaptic transmission / regulation of synaptic assembly at neuromuscular junction / male courtship behavior, veined wing generated song production / 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 / regulation of synaptic assembly at neuromuscular junction / male courtship behavior, veined wing generated song production / 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 | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.59 Å | |||||||||
![]() | Raisch T / Brockmann A / Ebbinghaus-Kintscher U / Freigang J / Gutbrod O / Kubicek J / Maertens B / Hofnagel O / Raunser S | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 109.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23 KB 23 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 17.3 KB | Display | ![]() |
Images | ![]() | 204.2 KB | ||
Others | ![]() ![]() ![]() ![]() | 29.1 MB 25.1 MB 165.3 MB 165.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7pxhMC ![]() 7pxeC ![]() 7pxfC ![]() 7pxgC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Sharpened by Phenix.Autosharpen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.7 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Density modified using Phenix.Resolve
File | emd_13703_additional_1.map | ||||||||||||
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Annotation | Density modified using Phenix.Resolve | ||||||||||||
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Density Histograms |
-Additional map: Sharpened using SPHIRE
File | emd_13703_additional_2.map | ||||||||||||
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Annotation | Sharpened using SPHIRE | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_13703_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_13703_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Slo tetramer
Entire | Name: Slo tetramer |
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Components |
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-Supramolecule #1: Slo tetramer
Supramolecule | Name: Slo tetramer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Isoform J of Calcium-activated potassium channel slowpoke
Macromolecule | Name: Isoform J of Calcium-activated potassium channel slowpoke type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 130.919094 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASGLIDTNF SSTLANGMSG CDQSTVESLA DDPTDSPFDA DDCLKVRKYW CFLLSSIFTF LAGLLVVLLW RAFAFVCCRK EPDLGPNDP KQKEQKASRN KQEFEGTFMT EAKDWAGELI SGQTTTGRIL VVLVFILSIA SLIIYFVDAS SEEVERCQKW S NNITQQID ...String: MASGLIDTNF SSTLANGMSG CDQSTVESLA DDPTDSPFDA DDCLKVRKYW CFLLSSIFTF LAGLLVVLLW RAFAFVCCRK EPDLGPNDP KQKEQKASRN KQEFEGTFMT EAKDWAGELI SGQTTTGRIL VVLVFILSIA SLIIYFVDAS SEEVERCQKW S NNITQQID LAFNIFFMVY FFIRFIAASD KLWFMLEMYS FVDYFTIPPS FVSIYLDRTW IGLRFLRALR LMTVPDILQY LN VLKTSSS IRLAQLVSIF ISVWLTAAGI IHLLENSGDP LDFDNAHRLS YWTCVYFLIV TMSTVGYGDV YCETVLGRTF LVF FLLVGL AIFASCIPEI IDLIGTRAKY GGTLKNEKGR RHIVVCGHIT YESVSHFLKD FLHEDREDVD VEVVFLHRKP PDLE LEGLF KRHFTTVEFF QGTIMNPIDL QRVKVHEADA CLVLANKYCQ DPDAEDAANI MRVISIKNYS DDIRVIIQLM QYHNK AYLL NIPSWDWKQG DDVICLAELK LGFIAQSCLA PGFSTMMANL FAMRSFKTSP DMQSWTNDYL RGTGMEMYTE TLSPTF IGI PFAQATELCF SKLKLLLLAI EIKGAEEGAD SKISINPRGA KIQANTQGFF IAQSADEVKR AWFYCKACHE DIKDETL IK KCKCKNLATF RKGVRAVQMV GRASDITRDR EDTNLLNRNV RRPNGTGNGT GGMHHMNNTA AAAAAAAAAG KQVNKVKP T VNVSRQVEGQ VISPSQYNRP TSRSSGTGTQ NQNGGVSLPA GIADDQSKDF DFEKTEMKYD STGMFHWSPA KSLEDCILD RNQAAMTVLN GHVVVCLFAD PDSPLIGLRN LVMPLRASNF HYHELKHVVI VGSVDYIRRE WKMLQNLPKI SVLNGSPLSR ADLRAVNVN LCDMCCILSA KVPSNDDPTL ADKEAILASL NIKAMTFDDT IGVLSQRGPE FDNLSATAGS PIVLQRRGSV Y GANVPMIT ELVNDGNVQF LDQDDDDDPD TELYLTQPFA CGTAFAVSVL DSLMSTTYFN QNALTLIRSL ITGGATPELE LI LAEGAGL RGGYSTVESL SNRDRCRVGQ ISLYDGPLAQ FGECGKYGDL FVAALKSYGM LCIGLYRFRD TSSSCDASSK RYV ITNPPD DFSLLPTDQV FVLMQFDPGL EYKPPAVRAP AGGRGTNTQG SGVGGGGSNK DDNS |
-Macromolecule #2: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 2 / Number of copies: 8 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #4: (4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-...
Macromolecule | Name: (4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM 4-OXIDE type: ligand / ID: 4 / Number of copies: 16 / Formula: 6PL |
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Molecular weight | Theoretical: 763.1 Da |
Chemical component information | ![]() ChemComp-6PL: |
-Macromolecule #5: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 4 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #6: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 6 / Number of copies: 6 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Macromolecule #7: (3~{S},6~{R},9~{S},12~{R},15~{S},18~{R},21~{S},24~{R})-4,6,10,16,...
Macromolecule | Name: (3~{S},6~{R},9~{S},12~{R},15~{S},18~{R},21~{S},24~{R})-4,6,10,16,18,22-hexamethyl-3,9,15,21-tetrakis(2-methylpropyl)-12,24-bis[(4-morpholin-4-ylphenyl)methyl]-1,7,13,19-tetraoxa-4,10,16,22- ...Name: (3~{S},6~{R},9~{S},12~{R},15~{S},18~{R},21~{S},24~{R})-4,6,10,16,18,22-hexamethyl-3,9,15,21-tetrakis(2-methylpropyl)-12,24-bis[(4-morpholin-4-ylphenyl)methyl]-1,7,13,19-tetraoxa-4,10,16,22-tetrazacyclotetracosane-2,5,8,11,14,17,20,23-octone type: ligand / ID: 7 / Number of copies: 1 / Formula: 8I2 |
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Molecular weight | Theoretical: 1.119388 KDa |
Chemical component information | ![]() ChemComp-8I2: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.7 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 75.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |