+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29665 | |||||||||
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Title | Cryo-EM structure of Nav1.7 with CBD | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Cryo-EM / sodium channel / VGSC / Nav1.7 / CBD / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / cardiac muscle cell action potential involved in contraction / locomotion / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / sodium channel inhibitor activity / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / detection of temperature stimulus involved in sensory perception of pain / behavioral response to pain / membrane depolarization / intercalated disc / sodium channel regulator activity / sodium ion transmembrane transport / cardiac muscle contraction / T-tubule / sensory perception of pain / post-embryonic development / axon guidance / positive regulation of neuron projection development / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to toxic substance / circadian rhythm / nervous system development / gene expression / response to heat / chemical synaptic transmission / perikaryon / transmembrane transporter binding / cell adhesion / inflammatory response / axon / synapse / extracellular region / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Fan X / Huang J / Yan N | |||||||||
Funding support | France, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Cannabidiol inhibits Na channels through two distinct binding sites. Authors: Jian Huang / Xiao Fan / Xueqin Jin / Sooyeon Jo / Hanxiong Bear Zhang / Akie Fujita / Bruce P Bean / Nieng Yan / Abstract: Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of ...Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Na1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Na1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Na1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated "wedged" position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29665.map.gz | 118 MB | EMDB map data format | |
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Header (meta data) | emd-29665-v30.xml emd-29665.xml | 19.9 KB 19.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_29665_fsc.xml | 10.5 KB | Display | FSC data file |
Images | emd_29665.png | 173.1 KB | ||
Masks | emd_29665_msk_1.map | 125 MB | Mask map | |
Others | emd_29665_half_map_1.map.gz emd_29665_half_map_2.map.gz | 116 MB 116 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29665 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29665 | HTTPS FTP |
-Validation report
Summary document | emd_29665_validation.pdf.gz | 962.4 KB | Display | EMDB validaton report |
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Full document | emd_29665_full_validation.pdf.gz | 962 KB | Display | |
Data in XML | emd_29665_validation.xml.gz | 19.1 KB | Display | |
Data in CIF | emd_29665_validation.cif.gz | 24.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29665 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29665 | HTTPS FTP |
-Related structure data
Related structure data | 8g1aMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_29665.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.114 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_29665_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_29665_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_29665_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human voltage-gated sodium channel Nav1.7 with beta subunits
+Supramolecule #1: Human voltage-gated sodium channel Nav1.7 with beta subunits
+Macromolecule #1: Sodium channel protein type 9 subunit alpha
+Macromolecule #2: Sodium channel subunit beta-1
+Macromolecule #3: Sodium channel subunit beta-2
+Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #6: cannabidiol
+Macromolecule #7: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phospho...
+Macromolecule #8: CHOLESTEROL HEMISUCCINATE
+Macromolecule #9: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]sp...
+Macromolecule #10: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #11: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |