+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9866 | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Rabbit Cav1.1-Nifedipine Complex | |||||||||||||||||||||
Map data | Rabbit Cav1.1-DHP Antagonist(Nifedipine) | |||||||||||||||||||||
Sample |
| |||||||||||||||||||||
Keywords | Membrane protein complex modulated by FDA approved drug. / MEMBRANE PROTEIN | |||||||||||||||||||||
Function / homology | Function and homology information positive regulation of muscle contraction / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / calcium ion import across plasma membrane / cellular response to caffeine / calcium channel regulator activity / regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated calcium channel activity / muscle contraction ...positive regulation of muscle contraction / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / calcium ion import across plasma membrane / cellular response to caffeine / calcium channel regulator activity / regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated calcium channel activity / muscle contraction / release of sequestered calcium ion into cytosol / T-tubule / calcium ion transmembrane transport / sarcolemma / transmembrane transporter binding / calmodulin binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||||||||||||||
Biological species | Oryctolagus cuniculus (rabbit) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||
Authors | Zhao Y / Huang G | |||||||||||||||||||||
Funding support | China, 6 items
| |||||||||||||||||||||
Citation | Journal: Cell / Year: 2019 Title: Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca Channel. Authors: Yanyu Zhao / Gaoxingyu Huang / Jianping Wu / Qiurong Wu / Shuai Gao / Zhen Yan / Jianlin Lei / Nieng Yan / Abstract: The L-type voltage-gated Ca (Ca) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been ...The L-type voltage-gated Ca (Ca) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been used for characterizing channel properties and for treatment of hypertension and other disorders. Here, we report the cryoelectron microscopy (cryo-EM) structures of Ca1.1 in complex with archetypal antagonistic drugs, nifedipine, diltiazem, and verapamil, at resolutions of 2.9 Å, 3.0 Å, and 2.7 Å, respectively, and with a DHP agonist Bay K 8644 at 2.8 Å. Diltiazem and verapamil traverse the central cavity of the pore domain, directly blocking ion permeation. Although nifedipine and Bay K 8644 occupy the same fenestration site at the interface of repeats III and IV, the coordination details support previous functional observations that Bay K 8644 is less favored in the inactivated state. These structures elucidate the modes of action of different Ca ligands and establish a framework for structure-guided drug discovery. | |||||||||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9866.map.gz | 116.2 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-9866-v30.xml emd-9866.xml | 19.2 KB 19.2 KB | Display Display | EMDB header |
Images | emd_9866.png | 14 KB | ||
Filedesc metadata | emd-9866.cif.gz | 8.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9866 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9866 | HTTPS FTP |
-Validation report
Summary document | emd_9866_validation.pdf.gz | 567.4 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_9866_full_validation.pdf.gz | 567 KB | Display | |
Data in XML | emd_9866_validation.xml.gz | 6.5 KB | Display | |
Data in CIF | emd_9866_validation.cif.gz | 7.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9866 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9866 | HTTPS FTP |
-Related structure data
Related structure data | 6jp5MC 9867C 9868C 9869C 6jp8C 6jpaC 6jpbC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_9866.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Rabbit Cav1.1-DHP Antagonist(Nifedipine) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.091 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
+Entire : Cav1.1-drug complex
+Supramolecule #1: Cav1.1-drug complex
+Supramolecule #2: Cav1.1-beta1a-alpha2-delta1-gamma complex
+Macromolecule #1: Voltage-dependent L-type calcium channel subunit alpha-1S
+Macromolecule #2: Voltage-dependent calcium channel gamma-1 subunit
+Macromolecule #3: Voltage-dependent calcium channel subunit alpha-2/delta-1
+Macromolecule #4: Voltage-dependent L-type calcium channel subunit beta-1
+Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #8: CALCIUM ION
+Macromolecule #9: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+Macromolecule #10: dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-d...
+Macromolecule #11: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #12: ETHANOLAMINE
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP |
---|---|
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 245171 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |