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Yorodumi- EMDB-23867: Human N-type voltage-gated calcium channel Cav2.2 in the presence... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23867 | |||||||||
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Title | Human N-type voltage-gated calcium channel Cav2.2 in the presence of ziconotide at 3.0 Angstrom resolution | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Cav2.2 / Channels / Calcium Ion-Selective / TRANSPORT PROTEIN-TOXIN complex / drugs | |||||||||
Function / homology | Function and homology information regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / host cell presynaptic membrane / cardiac muscle cell action potential involved in contraction / NCAM1 interactions ...regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / host cell presynaptic membrane / cardiac muscle cell action potential involved in contraction / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / ion channel inhibitor activity / neuromuscular junction development / calcium ion import across plasma membrane / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / response to amyloid-beta / regulation of calcium ion transport / calcium channel regulator activity / voltage-gated calcium channel activity / sarcoplasmic reticulum / protein localization to plasma membrane / Regulation of insulin secretion / modulation of chemical synaptic transmission / Adrenaline,noradrenaline inhibits insulin secretion / cellular response to amyloid-beta / calcium ion transport / T cell receptor signaling pathway / amyloid-beta binding / toxin activity / chemical synaptic transmission / neuronal cell body / calcium ion binding / synapse / extracellular exosome / extracellular region / ATP binding / membrane / metal ion binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Conus magus (magus cone) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Yan N / Gao S | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2021 Title: Structure of human Ca2.2 channel blocked by the painkiller ziconotide. Authors: Shuai Gao / Xia Yao / Nieng Yan / Abstract: The neuronal-type (N-type) voltage-gated calcium (Ca) channels, which are designated Ca2.2, have an important role in the release of neurotransmitters. Ziconotide is a Ca2.2-specific peptide pore ...The neuronal-type (N-type) voltage-gated calcium (Ca) channels, which are designated Ca2.2, have an important role in the release of neurotransmitters. Ziconotide is a Ca2.2-specific peptide pore blocker that has been clinically used for treating intractable pain. Here we present cryo-electron microscopy structures of human Ca2.2 (comprising the core α1 and the ancillary α2δ-1 and β3 subunits) in the presence or absence of ziconotide. Ziconotide is thoroughly coordinated by helices P1 and P2, which support the selectivity filter, and the extracellular loops (ECLs) in repeats II, III and IV of α1. To accommodate ziconotide, the ECL of repeat III and α2δ-1 have to tilt upward concertedly. Three of the voltage-sensing domains (VSDs) are in a depolarized state, whereas the VSD of repeat II exhibits a down conformation that is stabilized by Ca2-unique intracellular segments and a phosphatidylinositol 4,5-bisphosphate molecule. Our studies reveal the molecular basis for Ca2.2-specific pore blocking by ziconotide and establish the framework for investigating electromechanical coupling in Ca channels. | |||||||||
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_23867.map.gz | 78.3 MB | EMDB map data format | |
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Header (meta data) | emd-23867-v30.xml emd-23867.xml | 20.9 KB 20.9 KB | Display Display | EMDB header |
Images | emd_23867.png | 116.2 KB | ||
Filedesc metadata | emd-23867.cif.gz | 8.5 KB | ||
Others | emd_23867_additional_1.map.gz | 77.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23867 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23867 | HTTPS FTP |
-Validation report
Summary document | emd_23867_validation.pdf.gz | 569.1 KB | Display | EMDB validaton report |
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Full document | emd_23867_full_validation.pdf.gz | 568.6 KB | Display | |
Data in XML | emd_23867_validation.xml.gz | 6.3 KB | Display | |
Data in CIF | emd_23867_validation.cif.gz | 7.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23867 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23867 | HTTPS FTP |
-Related structure data
Related structure data | 7mixMC 7miyC C: citing same article (ref.) M: atomic model generated by this map |
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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_23867.map.gz / Format: CCP4 / Size: 83.7 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: 1.114 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: #1
File | emd_23867_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Cav2.2-ziconotide
+Supramolecule #1: Cav2.2-ziconotide
+Supramolecule #2: Cav2.2
+Macromolecule #1: Voltage-dependent N-type calcium channel subunit alpha-1B
+Macromolecule #2: Omega-conotoxin MVIIA
+Macromolecule #3: Voltage-dependent calcium channel subunit alpha-2/delta-1
+Macromolecule #4: Voltage-dependent L-type calcium channel subunit beta-3
+Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #9: CALCIUM ION
+Macromolecule #10: CHOLESTEROL HEMISUCCINATE
+Macromolecule #11: CHOLESTEROL
+Macromolecule #12: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+Macromolecule #13: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 20 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 6 seconds before plunging. |
Details | Cav2.2-ziconotide |
-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: 50.0 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: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 170839 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |