+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30851 | |||||||||
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Title | Voltage-gated sodium channel Nav1.1 and beta4 | |||||||||
Map data | voltage-gated sodium channel | |||||||||
Sample |
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Keywords | Voltage-gated sodium channel / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information regulation of sodium ion transmembrane transporter activity / AV node cell action potential / neuromuscular process controlling posture / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / axon initial segment / nerve development / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of sodium ion transport ...regulation of sodium ion transmembrane transporter activity / AV node cell action potential / neuromuscular process controlling posture / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / axon initial segment / nerve development / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of sodium ion transport / node of Ranvier / voltage-gated sodium channel complex / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / adult walking behavior / sodium ion transport / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / intercalated disc / neuronal action potential / sodium channel regulator activity / sodium ion transmembrane transport / detection of mechanical stimulus involved in sensory perception of pain / cardiac muscle contraction / T-tubule / establishment of localization in cell / determination of adult lifespan / Z disc / Sensory perception of sweet, bitter, and umami (glutamate) taste / transmembrane transporter binding / nuclear body / neuronal cell body / nucleoplasm / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Yan N / Pan X | |||||||||
Funding support | China, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2021 Title: Comparative structural analysis of human Na1.1 and Na1.5 reveals mutational hotspots for sodium channelopathies. Authors: Xiaojing Pan / Zhangqiang Li / Xueqin Jin / Yanyu Zhao / Gaoxingyu Huang / Xiaoshuang Huang / Zilin Shen / Yong Cao / Mengqiu Dong / Jianlin Lei / Nieng Yan / Abstract: Among the nine subtypes of human voltage-gated sodium (Na) channels, the brain and cardiac isoforms, Na1.1 and Na1.5, each carry more than 400 missense mutations respectively associated with epilepsy ...Among the nine subtypes of human voltage-gated sodium (Na) channels, the brain and cardiac isoforms, Na1.1 and Na1.5, each carry more than 400 missense mutations respectively associated with epilepsy and cardiac disorders. High-resolution structures are required for structure-function relationship dissection of the disease variants. We report the cryo-EM structures of the full-length human Na1.1-β4 complex at 3.3 Å resolution here and the Na1.5-E1784K variant in the accompanying paper. Up to 341 and 261 disease-related missense mutations in Na1.1 and Na1.5, respectively, are resolved. Comparative structural analysis reveals several clusters of disease mutations that are common to both Na1.1 and Na1.5. Among these, the majority of mutations on the extracellular loops above the pore domain and the supporting segments for the selectivity filter may impair structural integrity, while those on the pore domain and the voltage-sensing domains mostly interfere with electromechanical coupling and fast inactivation. Our systematic structural delineation of these mutations provides important insight into their pathogenic mechanism, which will facilitate the development of precise therapeutic interventions against various sodium channelopathies. | |||||||||
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_30851.map.gz | 28 MB | EMDB map data format | |
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Header (meta data) | emd-30851-v30.xml emd-30851.xml | 13 KB 13 KB | Display Display | EMDB header |
Images | emd_30851.png | 111.7 KB | ||
Filedesc metadata | emd-30851.cif.gz | 6.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30851 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30851 | HTTPS FTP |
-Validation report
Summary document | emd_30851_validation.pdf.gz | 550.3 KB | Display | EMDB validaton report |
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Full document | emd_30851_full_validation.pdf.gz | 549.9 KB | Display | |
Data in XML | emd_30851_validation.xml.gz | 5.6 KB | Display | |
Data in CIF | emd_30851_validation.cif.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30851 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30851 | HTTPS FTP |
-Related structure data
Related structure data | 7dtdMC 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_30851.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | voltage-gated sodium channel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0979 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 : Voltage-gated sodium channel
Entire | Name: Voltage-gated sodium channel |
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Components |
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-Supramolecule #1: Voltage-gated sodium channel
Supramolecule | Name: Voltage-gated sodium channel / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Sodium channel subunit beta-4
Macromolecule | Name: Sodium channel subunit beta-4 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.00098 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MPGAGDGGKA PARWLGTGLL GLFLLPVTLS LEVSVGKATD IYAVNGTEIL LPCTFSSCFG FEDLHFRWTY NSSDAFKILI EGTVKNEKS DPKVTLKDDD RITLVGSTKE KMNNISIVLR DLEFSDTGKY TCHVKNPKEN NLQHHATIFL QVVDRLEEVD N TVTLIILA ...String: MPGAGDGGKA PARWLGTGLL GLFLLPVTLS LEVSVGKATD IYAVNGTEIL LPCTFSSCFG FEDLHFRWTY NSSDAFKILI EGTVKNEKS DPKVTLKDDD RITLVGSTKE KMNNISIVLR DLEFSDTGKY TCHVKNPKEN NLQHHATIFL QVVDRLEEVD N TVTLIILA VVGGVIGLLI LILLIKKLII FILKKTREKK KECLVSSSGN DNTENGLPGS KAEEKPPSKV UniProtKB: Sodium channel subunit beta-4 |
-Macromolecule #2: Sodium channel protein type 1 subunit alpha
Macromolecule | Name: Sodium channel protein type 1 subunit alpha / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 233.796141 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMEQTVLV PPGPDSFNFF TRESLAAIER RIAEEKAKNP KPDKKDDDE NGPKPNSDLE AGKNLPFIYG DIPPEMVSEP LEDLDPYYIN KKTFIVLNKG KAIFRFSATS ALYILTPFNP L RKIAIKIL ...String: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMEQTVLV PPGPDSFNFF TRESLAAIER RIAEEKAKNP KPDKKDDDE NGPKPNSDLE AGKNLPFIYG DIPPEMVSEP LEDLDPYYIN KKTFIVLNKG KAIFRFSATS ALYILTPFNP L RKIAIKIL VHSLFSMLIM CTILTNCVFM TMSNPPDWTK NVEYTFTGIY TFESLIKIIA RGFCLEDFTF LRDPWNWLDF TV ITFAYVT EFVDLGNVSA LRTFRVLRAL KTISVIPGLK TIVGALIQSV KKLSDVMILT VFCLSVFALI GLQLFMGNLR NKC IQWPPT NASLEEHSIE KNITVNYNGT LINETVFEFD WKSYIQDSRY HYFLEGFLDA LLCGNSSDAG QCPEGYMCVK AGRN PNYGY TSFDTFSWAF LSLFRLMTQD FWENLYQLTL RAAGKTYMIF FVLVIFLGSF YLINLILAVV AMAYEEQNQA TLEEA EQKE AEFQQMIEQL KKQQEAAQQA ATATASEHSR EPSAAGRLSD SSSEASKLSS KSAKERRNRR KKRKQKEQSG GEEKDE DEF QKSESEDSIR RKGFRFSIEG NRLTYEKRYS SPHQSLLSIR GSLFSPRRNS RTSLFSFRGR AKDVGSENDF ADDEHST FE DNESRRDSLF VPRRHGERRN SNLSQTSRSS RMLAVFPANG KMHSTVDCNG VVSLVGGPSV PTSPVGQLLP EVIIDKPA T DDNGTTTETE MRKRRSSSFH VSMDFLEDPS QRQRAMSIAS ILTNTVEELE ESRQKCPPCW YKFSNIFLIW DCSPYWLKV KHVVNLVVMD PFVDLAITIC IVLNTLFMAM EHYPMTDHFN NVLTVGNLVF TGIFTAEMFL KIIAMDPYYY FQEGWNIFDG FIVTLSLVE LGLANVEGLS VLRSFRLLRV FKLAKSWPTL NMLIKIIGNS VGALGNLTLV LAIIVFIFAV VGMQLFGKSY K DCVCKIAS DCQLPRWHMN DFFHSFLIVF RVLCGEWIET MWDCMEVAGQ AMCLTVFMMV MVIGNLVVLN LFLALLLSSF SA DNLAATD DDNEMNNLQI AVDRMHKGVA YVKRKIYEFI QQSFIRKQKI LDEIKPLDDL NNKKDSCMSN HTAEIGKDLD YLK DVNGTT SGIGTGSSVE KYIIDESDYM SFINNPSLTV TVPIAVGESD FENLNTEDFS SESDLEESKE KLNESSSSSE GSTV DIGAP VEEQPVVEPE ETLEPEACFT EGCVQRFKCC QINVEEGRGK QWWNLRRTCF RIVEHNWFET FIVFMILLSS GALAF EDIY IDQRKTIKTM LEYADKVFTY IFILEMLLKW VAYGYQTYFT NAWCWLDFLI VDVSLVSLTA NALGYSELGA IKSLRT LRA LRPLRALSRF EGMRVVVNAL LGAIPSIMNV LLVCLIFWLI FSIMGVNLFA GKFYHCINTT TGDRFDIEDV NNHTDCL KL IERNETARWK NVKVNFDNVG FGYLSLLQVA TFKGWMDIMY AAVDSRNVEL QPKYEESLYM YLYFVIFIIF GSFFTLNL F IGVIIDNFNQ QKKKFGGQDI FMTEEQKKYY NAMKKLGSKK PQKPIPRPGN KFQGMVFDFV TRQVFDISIM ILICLNMVT MMVETDDQSE YVTTILSRIN LVFIVLFTGE CVLKLISLRH YYFTIGWNIF DFVVVILSIV GMFLAELIEK YFVSPTLFRV IRLARIGRI LRLIKGAKGI RTLLFALMMS LPALFNIGLL LFLVMFIYAI FGMSNFAYVK REVGIDDMFN FETFGNSMIC L FQITTSAG WDGLLAPILN SKPPDCDPNK VNPGSSVKGD CGNPSVGIFF FVSYIIISFL VVVNMYIAVI LENFSVATEE SA EPLSEDD FEMFYEVWEK FDPDATQFME FEKLSQFAAA LEPPLNLPQP NKLQLIAMDL PMVSGDRIHC LDILFAFTKR VLG ESGEMD ALRIQMEERF MASNPSKVSY QPITTTLKRK QEEVSAVIIQ RAYRRHLLKR TVKQASFTYN KNKIKGGANL LIKE DMIID RINENSITEK TDLTMSTAAC PPSYDRVTKP IVEKHEQEGK DEKAKGK UniProtKB: Sodium channel protein type 1 subunit alpha |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #4: (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: 4 / Number of copies: 1 / 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
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 K3 (6k x 4k) / 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 |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 133127 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |