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- PDB-8fhs: Human L-type voltage-gated calcium channel Cav1.2 in the presence... -
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Basic information
Entry | Database: PDB / ID: 8fhs | |||||||||||||||||||||||||||||||||
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Title | Human L-type voltage-gated calcium channel Cav1.2 in the presence of amiodarone and sofosbuvir at 3.3 Angstrom resolution | |||||||||||||||||||||||||||||||||
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![]() | TRANSPORT PROTEIN / Cav1.2 / Channels / Calcium Ion-Selective | |||||||||||||||||||||||||||||||||
Function / homology | ![]() 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 / positive regulation of adenylate cyclase activity / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel ...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 / positive regulation of adenylate cyclase activity / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during AV node cell action potential / high voltage-gated calcium channel activity / membrane depolarization during bundle of His cell action potential / cardiac conduction / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of muscle contraction / cell communication by electrical coupling involved in cardiac conduction / regulation of ventricular cardiac muscle cell action potential / regulation of ventricular cardiac muscle cell membrane repolarization / NCAM1 interactions / camera-type eye development / cardiac muscle cell action potential involved in contraction / embryonic forelimb morphogenesis / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / neuronal dense core vesicle / Phase 0 - rapid depolarisation / alpha-actinin binding / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / calcium ion import across plasma membrane / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / voltage-gated calcium channel activity / presynaptic active zone membrane / calcium channel regulator activity / sarcoplasmic reticulum / protein localization to plasma membrane / GABA-ergic synapse / Regulation of insulin secretion / postsynaptic density membrane / calcium ion transmembrane transport / Z disc / cellular response to amyloid-beta / Adrenaline,noradrenaline inhibits insulin secretion / calcium ion transport / T cell receptor signaling pathway / heart development / positive regulation of cytosolic calcium ion concentration / chemical synaptic transmission / perikaryon / calmodulin binding / postsynaptic density / cilium / synapse / dendrite / extracellular exosome / nucleoplasm / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||||||||||||||
![]() | Gao, S. / Yao, X. / Yan, N. | |||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for human Ca1.2 inhibition by multiple drugs and the neurotoxin calciseptine. Authors: Shuai Gao / Xia Yao / Jiaofeng Chen / Gaoxingyu Huang / Xiao Fan / Lingfeng Xue / Zhangqiang Li / Tong Wu / Yupeng Zheng / Jian Huang / Xueqin Jin / Yan Wang / Zhifei Wang / Yong Yu / Lei ...Authors: Shuai Gao / Xia Yao / Jiaofeng Chen / Gaoxingyu Huang / Xiao Fan / Lingfeng Xue / Zhangqiang Li / Tong Wu / Yupeng Zheng / Jian Huang / Xueqin Jin / Yan Wang / Zhifei Wang / Yong Yu / Lei Liu / Xiaojing Pan / Chen Song / Nieng Yan / ![]() ![]() Abstract: Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well ...Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na channels, a series of structural changes occur, including upward movement of VSD coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5 merges with S5 to become a single helix, resulting in a widened but still non-conductive intracellular gate. | |||||||||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 555.6 KB | Display | ![]() |
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PDB format | ![]() | 430.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.1 MB | Display | ![]() |
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Full document | ![]() | 2.2 MB | Display | |
Data in XML | ![]() | 79.4 KB | Display | |
Data in CIF | ![]() | 117.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 29102MC ![]() 8we6C ![]() 8we7C ![]() 8we8C ![]() 8we9C ![]() 8weaC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Voltage-dependent L-type calcium channel subunit ... , 2 types, 2 molecules AC
#1: Protein | Mass: 249242.219 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#3: Protein | Mass: 54607.852 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein , 1 types, 1 molecules D
#2: Protein | Mass: 124692.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 4 types, 7 molecules 
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||||
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#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #12: Sugar | |
-Non-polymers , 5 types, 10 molecules 








#7: Chemical | #8: Chemical | ChemComp-BBI / ( | #9: Chemical | ChemComp-WG6 / | #10: Chemical | #11: Chemical | ChemComp-CLR / |
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-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Cav1.2 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2100 nm / Nominal defocus min: 1900 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 88794 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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