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Yorodumi- PDB-7wli: CryoEM structure of human low-voltage activated T-type calcium ch... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7wli | ||||||
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Title | CryoEM structure of human low-voltage activated T-type calcium channel CaV3.3 (apo) | ||||||
Components | Voltage-dependent T-type calcium channel subunit alpha-1I | ||||||
Keywords | MEMBRANE PROTEIN / apo state | ||||||
Function / homology | Function and homology information high voltage-gated calcium channel activity / sleep / NCAM1 interactions / voltage-gated calcium channel complex / calcium ion import across plasma membrane / neuronal action potential / Smooth Muscle Contraction / voltage-gated calcium channel activity / signal transduction / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | He, L. / Yu, Z. / Dong, Y. / Chen, Q. / Zhao, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structure, gating, and pharmacology of human Ca3.3 channel. Authors: Lingli He / Zhuoya Yu / Ze Geng / Zhuo Huang / Changjiang Zhang / Yanli Dong / Yiwei Gao / Yuhang Wang / Qihao Chen / Le Sun / Xinyue Ma / Bo Huang / Xiaoqun Wang / Yan Zhao / Abstract: The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been ...The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been implicated with many diseases. Here, we determine structures of the human T-type Ca3.3 channel, in the absence and presence of antihypertensive drug mibefradil, antispasmodic drug otilonium bromide and antipsychotic drug pimozide. Ca3.3 contains a long bended S6 helix from domain III, with a positive charged region protruding into the cytosol, which is critical for T-type Ca channel activation at low voltage. The drug-bound structures clearly illustrate how these structurally different compounds bind to the same central cavity inside the Ca3.3 channel, but are mediated by significantly distinct interactions between drugs and their surrounding residues. Phospholipid molecules penetrate into the central cavity in various extent to shape the binding pocket and play important roles in stabilizing the inhibitor. These structures elucidate mechanisms of channel gating, drug recognition, and actions, thus pointing the way to developing potent and subtype-specific drug for therapeutic treatments of related disorders. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wli.cif.gz | 249.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wli.ent.gz | 182.1 KB | Display | PDB format |
PDBx/mmJSON format | 7wli.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wli_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7wli_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7wli_validation.xml.gz | 41.4 KB | Display | |
Data in CIF | 7wli_validation.cif.gz | 60.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wl/7wli ftp://data.pdbj.org/pub/pdb/validation_reports/wl/7wli | HTTPS FTP |
-Related structure data
Related structure data | 32584MC 7wljC 7wlkC 7wllC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 245373.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CACNA1I, KIAA1120 / Production host: Homo sapiens (human) / References: UniProt: Q9P0X4 | ||||||||||
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#2: Chemical | #3: Sugar | #4: Chemical | ChemComp-3PE / #5: Chemical | ChemComp-Y01 / Has ligand of interest | N | 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 |
-Sample preparation
Component | Name: CaV3.3 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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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 |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 9.6 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 93988 / Symmetry type: POINT |