+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20951 | |||||||||
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Title | Cardiac sodium channel | |||||||||
Map data | CryoEM map of sodium channel structure | |||||||||
Sample |
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Function / homology | Function and homology information voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation ...voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation / regulation of ventricular cardiac muscle cell membrane depolarization / cardiac ventricle development / membrane depolarization during atrial cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transport / brainstem development / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / positive regulation of action potential / atrial cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / telencephalon development / regulation of atrial cardiac muscle cell membrane depolarization / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / membrane depolarization during action potential / ventricular cardiac muscle cell action potential / sodium ion import across plasma membrane / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / voltage-gated sodium channel complex / regulation of cardiac muscle cell contraction / voltage-gated sodium channel activity / ankyrin binding / positive regulation of heart rate / sodium ion transport / nitric-oxide synthase binding / fibroblast growth factor binding / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / neuronal action potential / lateral plasma membrane / sodium ion transmembrane transport / cardiac muscle contraction / positive regulation of epithelial cell proliferation / T-tubule / cellular response to calcium ion / regulation of heart rate / cerebellum development / caveola / response to organic cyclic compound / sarcolemma / Z disc / serine-type endopeptidase inhibitor activity / scaffold protein binding / transmembrane transporter binding / calmodulin binding / protein domain specific binding / axon / ubiquitin protein ligase binding / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / extracellular space / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Aequorea victoria (jellyfish) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Jiang D / Shi H / Tonggu L / Lenaeus MJ / Zheng N / Catterall WA | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell / Year: 2020 Title: Structure of the Cardiac Sodium Channel. Authors: Daohua Jiang / Hui Shi / Lige Tonggu / Tamer M Gamal El-Din / Michael J Lenaeus / Yan Zhao / Craig Yoshioka / Ning Zheng / William A Catterall / Abstract: Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other ...Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other sodium channels by a unique glycosyl moiety and loss of disulfide-bonding capability at the Naβ subunit-interaction sites. The antiarrhythmic drug flecainide specifically targets the central cavity of the pore. The voltage sensors are partially activated, and the fast-inactivation gate is partially closed. Activation of the voltage sensor of Domain III allows binding of the isoleucine-phenylalanine-methionine (IFM) motif to the inactivation-gate receptor. Asp and Ala, in the selectivity motif DEKA, line the walls of the ion-selectivity filter, whereas Glu and Lys are in positions to accept and release Na ions via a charge-delocalization network. Arrhythmia mutation sites undergo large translocations during gating, providing a potential mechanism for pathogenic effects. Our results provide detailed insights into Na1.5 structure, pharmacology, activation, inactivation, ion selectivity, and arrhythmias. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20951.map.gz | 59.4 MB | EMDB map data format | |
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Header (meta data) | emd-20951-v30.xml emd-20951.xml | 18.5 KB 18.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20951_fsc.xml | 7.2 KB | Display | FSC data file |
Images | emd_20951.png | 55.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20951 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20951 | HTTPS FTP |
-Validation report
Summary document | emd_20951_validation.pdf.gz | 571.1 KB | Display | EMDB validaton report |
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Full document | emd_20951_full_validation.pdf.gz | 570.6 KB | Display | |
Data in XML | emd_20951_validation.xml.gz | 10.6 KB | Display | |
Data in CIF | emd_20951_validation.cif.gz | 13.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20951 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20951 | HTTPS FTP |
-Related structure data
Related structure data | 6uz3MC 6uz0C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20951.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | CryoEM map of sodium channel structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.056 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : cardiac sodium channel apo structure
Entire | Name: cardiac sodium channel apo structure |
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Components |
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-Supramolecule #1: cardiac sodium channel apo structure
Supramolecule | Name: cardiac sodium channel apo structure / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) / Organ: heart |
Recombinant expression | Organism: Mammalian 1 orthobornavirus / Recombinant strain: HEK293 / Recombinant plasmid: pEG_BacMam |
Molecular weight | Theoretical: 250 KDa |
-Macromolecule #1: Sodium channel protein type 5 subunit alpha,Green fluorescent protein
Macromolecule | Name: Sodium channel protein type 5 subunit alpha,Green fluorescent protein type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Aequorea victoria (jellyfish) / Organ: heart |
Molecular weight | Theoretical: 209.037781 KDa |
Recombinant expression | Organism: Mammalian 1 orthobornavirus |
Sequence | String: MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE EAPRPQLDLQ ASKKLPDLYG NPPRELIGEP LEDLDPFYS TQKTFIVLNK GKTIFRFSAT NALYVLSPFH PVRRAAVKIL VHSLFSMLIM CTILTNCVFM AQHDPPPWTK Y VEYTFTAI ...String: MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE EAPRPQLDLQ ASKKLPDLYG NPPRELIGEP LEDLDPFYS TQKTFIVLNK GKTIFRFSAT NALYVLSPFH PVRRAAVKIL VHSLFSMLIM CTILTNCVFM AQHDPPPWTK Y VEYTFTAI YTFESLVKIL ARGFCLHAFT FLRDPWNWLD FSVIVMAYTT EFVDLGNVSA LRTFRVLRAL KTISVISGLK TI VGALIQS VKKLADVMVL TVFCLSVFAL IGLQLFMGNL RHKCVRNFTE LNGTNGSVEA DGLVWNSLDV YLNDPANYLL KNG TTDVLL CGNSSDAGTC PEGYRCLKAG ENPDHGYTSF DSFAWAFLAL FRLMTQDCWE RLYQQTLRSA GKIYMIFFML VIFL GSFYL VNLILAVVAM AYEEQNQATI AETEEKEKRF QEAMEMLKKE HEALTIRGVD TVSRSSARQR ALSAVSVLTS ALEEL EESH RKCPPCWNRF AQHYLIWECC PLWMSIKQKV KFVVMDPFAD LTITMCIVLN TLFMALEHYN MTAEFEEMLQ VGNLVF TGI FTAEMTFKII ALDPYYYFQQ GWNIFDSIIV ILSLMELGLS RMGNLSVLRS FRLLRVFKLA KSWPTLNTLI KIIGNSV GA LGNLTLVLAI IVFIFAVVGM QLFGKNYSEL RHRISDSGLL PRWHMMDFFH AFLIIFRILC GEWIETMWDC MEVSGQSL C LLVFLLVMVI GNLVVLNLFL ALLLSSFSAD NLTAPDEDGE MNNLQLALAR IQRGLRFVKR TTWDFCCGIL RRRPKKPAA LATHSQLPSC ITAPRSPPPP EVEKVPPARK ETRFEEDKRP GQGTPGDSEP VCVPIAVAES DTEDQEEDEE NGKVWWRLRK TCYRIVEHS WFETFIIFMI LLSSGALAFE DIYLEERKTI KVLLEYADKM FTYVFVLEML LKWVAYGFKK YFTNAWCWLD F LIVDVSLV SLVANTLGFA EMGPIKSLRT LRALRPLRAL SRFEGMRVVV NALVGAIPSI MNVLLVCLIF WLIFSIMGVN LF AGKFGRC INQTEGDLPL NYTIVNNKSE CESFNVTGEL YWTKVKVNFD NVGAGYLALL QVATFKGWMD IMYAAVDSRG YEE QPQWED NLYMYIYFVV FIIFGSFFTL NLFIGVIIDN FNQQKKKLGG QDIFMTEEQK KYYNAMKKLG SKKPQKPIPR PLNK YQGFI FDIVTKQAFD VTIMFLICLN MVTMMVETDD QSPEKVNILA KINLLFVAIF TGECIVKMAA LRHYYFTNSW NIFDF VVVI LSIVGTVLSD IIQKYFFSPT LFRVIRLARI GRILRLIRGA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI YSIFGM ANF AYVKWEAGID DMFNFQTFAN SMLCLFQITT SAGWDGLLSP ILNTGPPYCD PNLPNSNGSR GNCGSPAVGI LFFTTYI II SFLIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW EKFDPEATQF IEYLALSDFA DALSEPLRIA KPNQISLI N MDLPMVSGDR IHCMDILFAF TKRVLGESGE MDALKIQMEE KFMAANPSKI SYEPITTTLE VLFQGPGSMV SKGEELFTG VVPILVELDG DVNGHKFSVS GEGEGDATYG KLTLKFICTT GKLPVPWPTL VTTLTYGVQC FSRYPDHMKQ HDFFKSAMPE GYVQERTIF FKDDGNYKTR AEVKFEGDTL VNRIELKGID FKEDGNILGH KLEYNYNSHN VYIMADKQKN GIKVNFKIRH N IEDGSVQL ADHYQQNTPI GDGPVLLPDN HYLSTQSALS KDPNEKRDHM VLLEFVTAAG ITLGMDELYK GSDYKDDDDK |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #5: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]sp...
Macromolecule | Name: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en type: ligand / ID: 5 / Number of copies: 5 / Formula: 9Z9 |
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Molecular weight | Theoretical: 544.805 Da |
Chemical component information | ChemComp-9Z9: |
-Macromolecule #6: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyl...
Macromolecule | Name: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate type: ligand / ID: 6 / Number of copies: 11 / Formula: 6OU |
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Molecular weight | Theoretical: 717.996 Da |
Chemical component information | ChemComp-6OU: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.5 mg/mL | |||||||||
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Buffer | pH: 6 Component:
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Grid | Model: UltrAuFoil / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV Details: waiting for 20s, blot for 2.5-3.5s before plunging. | |||||||||
Details | This sample include channel protein solubilized with GDN detergent. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 95.0 K / Max: 103.0 K |
Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Details | Squares on grids were manually screened before data collection |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-40 / Number grids imaged: 6 / Number real images: 7400 / Average exposure time: 8.0 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus max: 3.0 µm / Calibrated defocus min: 1.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.8 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |