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- EMDB-31960: Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-b... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31960 | |||||||||
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Title | Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-beta1 complex, bound to PD173212 | |||||||||
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Function / homology | ![]() 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 / positive regulation of muscle contraction / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in 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 / positive regulation of muscle contraction / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / 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 / neuromuscular junction development / calcium ion import across plasma membrane / Phase 0 - rapid depolarisation / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / response to amyloid-beta / regulation of calcium ion transport / voltage-gated calcium channel activity / T-tubule / 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 | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Dong Y / Gao Y / Wang Y / Zhao Y | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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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 | ![]() | 117.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.4 KB 18.4 KB | Display Display | ![]() |
Images | ![]() | 113.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vfvMC ![]() 7vfsC ![]() 7vfuC ![]() 7vfwC 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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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : CaV2.2-alpha2delta1-beta1 complex
+Supramolecule #1: CaV2.2-alpha2delta1-beta1 complex
+Macromolecule #1: Voltage-dependent N-type calcium channel subunit alpha-1B
+Macromolecule #2: Voltage-dependent calcium channel subunit alpha-2/delta-1
+Macromolecule #3: Voltage-dependent L-type calcium channel subunit beta-1
+Macromolecule #6: HEXADECANE
+Macromolecule #7: CHOLESTEROL HEMISUCCINATE
+Macromolecule #8: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...
+Macromolecule #9: (2~{S})-~{N}-[(2~{S})-1-(~{tert}-butylamino)-1-oxidanylidene-3-(4...
+Macromolecule #10: CALCIUM ION
+Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
-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: 7.5 |
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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 K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 9.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |