+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31519 | |||||||||
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Title | structure of a channel | |||||||||
Map data | Cryo-EM map of a channel | |||||||||
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 / cardiac ventricle development / regulation of ventricular cardiac muscle cell membrane depolarization / regulation of atrial cardiac muscle cell membrane repolarization / membrane depolarization during atrial cardiac muscle cell action potential / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transport / brainstem development / membrane depolarization during AV node cell action potential / voltage-gated sodium channel activity involved in cardiac muscle 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 / sodium ion import across plasma membrane / ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / voltage-gated sodium channel activity / ankyrin binding / sodium ion transport / positive regulation of heart rate / nitric-oxide synthase binding / fibroblast growth factor binding / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / sodium ion transmembrane transport / lateral plasma membrane / neuronal action potential / cardiac muscle contraction / T-tubule / cellular response to calcium ion / regulation of heart rate / bioluminescence / cerebellum development / generation of precursor metabolites and energy / caveola / positive regulation of epithelial cell proliferation / response to organic cyclic compound / sarcolemma / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / symbiont entry into host cell / protein domain specific binding / axon / viral envelope / ubiquitin protein ligase binding / virion attachment to host cell / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Recombinant vesicular stomatitis Indiana virus rVSV-G/GFP | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Jiang DJ / Catterall WA | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell / Year: 2021 Title: Open-state structure and pore gating mechanism of the cardiac sodium channel. Authors: Daohua Jiang / Richard Banh / Tamer M Gamal El-Din / Lige Tonggu / Michael J Lenaeus / Régis Pomès / Ning Zheng / William A Catterall / Abstract: The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, ...The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, we blocked fast inactivation with a mutation and captured the elusive open-state structure. The fast inactivation gate moves away from its receptor, allowing asymmetric opening of pore-lining S6 segments, which bend and rotate at their intracellular ends to dilate the activation gate to ∼10 Å diameter. Molecular dynamics analyses predict physiological rates of Na conductance. The open-state pore blocker propafenone binds in a high-affinity pose, and drug-access pathways are revealed through the open activation gate and fenestrations. Comparison with mutagenesis results provides a structural map of arrhythmia mutations that target the activation and fast inactivation gates. These results give atomic-level insights into molecular events that underlie generation of the action potential, open-state drug block, and fast inactivation of cardiac sodium channels, which initiate the heartbeat. | |||||||||
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_31519.map.gz | 117.9 MB | EMDB map data format | |
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Header (meta data) | emd-31519-v30.xml emd-31519.xml | 14 KB 14 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_31519_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_31519.png | 71 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31519 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31519 | HTTPS FTP |
-Validation report
Summary document | emd_31519_validation.pdf.gz | 456.7 KB | Display | EMDB validaton report |
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Full document | emd_31519_full_validation.pdf.gz | 456.2 KB | Display | |
Data in XML | emd_31519_validation.xml.gz | 11.6 KB | Display | |
Data in CIF | emd_31519_validation.cif.gz | 15.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31519 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31519 | HTTPS FTP |
-Related structure data
Related structure data | 7fbsMC M: atomic model generated by this map C: citing same article (ref.) |
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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_31519.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM map of a channel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 : sodium channel with four homologous domains
Entire | Name: sodium channel with four homologous domains |
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Components |
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-Supramolecule #1: sodium channel with four homologous domains
Supramolecule | Name: sodium channel with four homologous domains / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Mammalian 1 orthobornavirus |
Molecular weight | Theoretical: 250 KDa |
-Macromolecule #1: Sodium channel protein type 5 subunit alpha,Sodium channel protei...
Macromolecule | Name: Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,G protein/GFP fusion protein type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Recombinant vesicular stomatitis Indiana virus rVSV-G/GFP |
Molecular weight | Theoretical: 209.030625 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 QDQQQTEEQK 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 #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 3 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #3: [(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: 3 / Number of copies: 11 / Formula: 6OU |
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Molecular weight | Theoretical: 717.996 Da |
Chemical component information | ChemComp-6OU: |
-Macromolecule #4: 1-[2-[(2R)-2-oxidanyl-3-(propylamino)propoxy]phenyl]-3-phenyl-pro...
Macromolecule | Name: 1-[2-[(2R)-2-oxidanyl-3-(propylamino)propoxy]phenyl]-3-phenyl-propan-1-one type: ligand / ID: 4 / Number of copies: 1 / Formula: 4Y4 |
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Molecular weight | Theoretical: 341.444 Da |
Chemical component information | ChemComp-4Y4: |
-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: 2 / Formula: 9Z9 |
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Molecular weight | Theoretical: 544.805 Da |
Chemical component information | ChemComp-9Z9: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 6 |
Grid | Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum ER / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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Output model | PDB-7fbs: |