[English] 日本語
Yorodumi- PDB-7vfs: Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-b... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7vfs | ||||||
---|---|---|---|---|---|---|---|
Title | Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-beta1 complex, apo state | ||||||
Components | (Voltage-dependent ...) x 3 | ||||||
Keywords | MEMBRANE PROTEIN / Voltage gated calcium channel / N-type / complex | ||||||
Function / homology | Function and homology information positive regulation of muscle contraction / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in contraction / high voltage-gated calcium channel activity ...positive regulation of muscle contraction / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in contraction / high voltage-gated calcium channel activity / 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 / neuromuscular junction development / voltage-gated calcium channel complex / neuronal dense core vesicle / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / calcium ion import across plasma membrane / regulation of calcium ion transport / response to amyloid-beta / voltage-gated calcium channel activity / sarcoplasmic reticulum / calcium ion transmembrane transport / modulation of chemical synaptic transmission / cellular response to amyloid-beta / calcium ion transport / amyloid-beta binding / chemical synaptic transmission / neuronal cell body / synapse / calcium ion binding / extracellular exosome / ATP binding / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Dong, Y. / Gao, Y. / Wang, Y. / Zhao, Y. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Cell Rep / Year: 2021 Title: Closed-state inactivation and pore-blocker modulation mechanisms of human Ca2.2. Authors: Yanli Dong / Yiwei Gao / Shuai Xu / Yuhang Wang / Zhuoya Yu / Yue Li / Bin Li / Tian Yuan / Bei Yang / Xuejun Cai Zhang / Daohua Jiang / Zhuo Huang / Yan Zhao / Abstract: N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and ...N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human Ca2.2 complex in apo, ziconotide-bound, and two Ca2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP) molecule, which is distinct from the other three VSDs of Ca2.2, as well as activated VSDs observed in previous structures of Ca channels. This structure reveals the molecular basis for the unique inactivation process of Ca2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7vfs.cif.gz | 474.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7vfs.ent.gz | 377.7 KB | Display | PDB format |
PDBx/mmJSON format | 7vfs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vf/7vfs ftp://data.pdbj.org/pub/pdb/validation_reports/vf/7vfs | HTTPS FTP |
---|
-Related structure data
Related structure data | 31958MC 7vfuC 7vfvC 7vfwC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Voltage-dependent ... , 3 types, 3 molecules ABD
#1: Protein | Mass: 262831.781 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CACNA1B, CACH5, CACNL1A5 / Production host: Homo sapiens (human) / References: UniProt: Q00975 |
---|---|
#2: Protein | Mass: 124692.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CACNA2D1, CACNL2A, CCHL2A, MHS3 / Production host: Homo sapiens (human) / References: UniProt: P54289 |
#3: Protein | Mass: 65799.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CACNB1, CACNLB1 / Production host: Homo sapiens (human) / References: UniProt: Q02641 |
-Sugars , 3 types, 11 molecules
#4: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Polysaccharide | beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #10: Sugar | ChemComp-NAG / |
---|
-Non-polymers , 4 types, 24 molecules
#6: Chemical | ChemComp-R16 / #7: Chemical | #8: Chemical | ChemComp-PT5 / [( | #9: Chemical | |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: CaV2.2-alpha2delta1-beta1 complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 9.6 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 253920 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|