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Yorodumi- EMDB-29004: Structure of the human L-type voltage-gated calcium channel Cav1.... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29004 | |||||||||
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Title | Structure of the human L-type voltage-gated calcium channel Cav1.2 complexed with gabapentin | |||||||||
Map data | CaV1.2_GBN_composite_map_DLM | |||||||||
Sample |
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Keywords | voltage-gated calcium channel / CaV alpha2delta / drug binding / gabapentin / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / positive regulation of high voltage-gated calcium channel activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during AV node cell action potential / positive regulation of adenylate cyclase activity ...voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / positive regulation of high voltage-gated calcium channel activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during AV node cell action potential / positive regulation of adenylate cyclase activity / high voltage-gated calcium channel activity / cardiac conduction / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / cell communication by electrical coupling involved in cardiac conduction / regulation of ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / camera-type eye development / NCAM1 interactions / embryonic forelimb morphogenesis / calcium ion transport into cytosol / voltage-gated calcium channel complex / calcium ion import across plasma membrane / Phase 0 - rapid depolarisation / alpha-actinin binding / regulation of heart rate by cardiac conduction / calcium channel regulator activity / voltage-gated calcium channel activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / T-tubule / Regulation of insulin secretion / calcium ion transmembrane transport / postsynaptic density membrane / Z disc / Adrenaline,noradrenaline inhibits insulin secretion / heart development / positive regulation of cytosolic calcium ion concentration / perikaryon / postsynaptic density / calmodulin binding / dendrite / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Oryctolagus cuniculus (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Chen Z / Mondal A / Minor DL | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2023 Title: Structural basis for Caαδ:gabapentin binding. Authors: Zhou Chen / Abhisek Mondal / Daniel L Minor / Abstract: Gabapentinoid drugs for pain and anxiety act on the Caαδ-1 and Caαδ-2 subunits of high-voltage-activated calcium channels (Ca1s and Ca2s). Here we present the cryo-EM structure of the gabapentin- ...Gabapentinoid drugs for pain and anxiety act on the Caαδ-1 and Caαδ-2 subunits of high-voltage-activated calcium channels (Ca1s and Ca2s). Here we present the cryo-EM structure of the gabapentin-bound brain and cardiac Ca1.2/Caβ/Caαδ-1 channel. The data reveal a binding pocket in the Caαδ-1 dCache1 domain that completely encapsulates gabapentin and define Caαδ isoform sequence variations that explain the gabapentin binding selectivity of Caαδ-1 and Caαδ-2. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29004.map.gz | 258.4 MB | EMDB map data format | |
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Header (meta data) | emd-29004-v30.xml emd-29004.xml | 21.5 KB 21.5 KB | Display Display | EMDB header |
Images | emd_29004.png | 115.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29004 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29004 | HTTPS FTP |
-Validation report
Summary document | emd_29004_validation.pdf.gz | 468.5 KB | Display | EMDB validaton report |
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Full document | emd_29004_full_validation.pdf.gz | 468.1 KB | Display | |
Data in XML | emd_29004_validation.xml.gz | 7.8 KB | Display | |
Data in CIF | emd_29004_validation.cif.gz | 8.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29004 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29004 | HTTPS FTP |
-Related structure data
Related structure data | 8fd7MC C: citing same article (ref.) M: atomic model generated by this map |
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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_29004.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | CaV1.2_GBN_composite_map_DLM | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.835 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : Ternary complex of human CaV alpha1C with rabbit CaV alpha2delta-...
+Supramolecule #1: Ternary complex of human CaV alpha1C with rabbit CaV alpha2delta-...
+Supramolecule #2: Human CaV alpha1C
+Supramolecule #3: Rabbit CaV alpha2delta-1
+Supramolecule #4: Rabbit CaV beta3
+Macromolecule #1: Voltage-dependent calcium channel subunit alpha-2/delta-1
+Macromolecule #2: Voltage-dependent L-type calcium channel subunit alpha-1C
+Macromolecule #3: Voltage-dependent L-type calcium channel subunit beta-3
+Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #6: [1-(AMINOMETHYL)CYCLOHEXYL]ACETIC ACID
+Macromolecule #7: CALCIUM ION
+Macromolecule #8: SODIUM ION
+Macromolecule #9: (2R)-3-{[(R)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(dodecanoy...
+Macromolecule #10: (2S)-3-{[(R)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(dodecanoy...
+Macromolecule #11: CHOLESTEROL
+Macromolecule #12: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2.0 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 46.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.7 µm / Nominal defocus min: 0.9 µm / Nominal magnification: 105000 |
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 | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 259107 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |