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- EMDB-9782: Structure of human voltage-gated sodium channel Nav1.7 in complex... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9782 | ||||||||||||||||||
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Title | Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, ProTx-II and tetrodotoxin | ||||||||||||||||||
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Function / homology | ![]() 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 / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / 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 / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / 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 / regulation of ventricular cardiac muscle cell membrane repolarization / locomotion / sodium channel inhibitor activity / voltage-gated sodium channel complex / neuronal action potential propagation / membrane depolarization during action potential / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / behavioral response to pain / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / membrane depolarization / detection of temperature stimulus involved in sensory perception of pain / intercalated disc / sodium ion transmembrane transport / sodium channel regulator activity / neuronal action potential / cardiac muscle contraction / sensory perception of pain / T-tubule / post-embryonic development / axon guidance / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of neuron projection development / 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 | ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||||||||
![]() | Shen H / Liu D / Lei J / Yan N | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of human Na1.7 channel in complex with auxiliary subunits and animal toxins. Authors: Huaizong Shen / Dongliang Liu / Kun Wu / Jianlin Lei / Nieng Yan / ![]() Abstract: Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations ...Voltage-gated sodium channel Na1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSD), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSD The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na1.7 and establish the foundation for structure-aided development of analgesics. | ||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 49.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.4 KB 15.4 KB | Display Display | ![]() |
Images | ![]() | 113.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 475.9 KB | Display | ![]() |
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Full document | ![]() | 475.5 KB | Display | |
Data in XML | ![]() | 6 KB | Display | |
Data in CIF | ![]() | 6.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6j8iMC ![]() 6j8jMC ![]() 9781C ![]() 6j8gC ![]() 6j8hC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.091 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Complex of human voltage-gated sodium channel Nav1.7 with auxilia...
Entire | Name: Complex of human voltage-gated sodium channel Nav1.7 with auxiliary beta subunits, ProTx-II and tetrodotoxin |
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Components |
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-Supramolecule #1: Complex of human voltage-gated sodium channel Nav1.7 with auxilia...
Supramolecule | Name: Complex of human voltage-gated sodium channel Nav1.7 with auxiliary beta subunits, ProTx-II and tetrodotoxin type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Sodium channel subunit beta-2
Macromolecule | Name: Sodium channel subunit beta-2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.355859 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MHRDAWLPRP AFSLTGLSLF FSLVPPGRSM EVTVPATLNV LNGSDARLPC TFNSCYTVNH KQFSLNWTYQ ECNNCSEEMF LQFRMKIIN LKLERFQDRV EFSGNPSKYD VSVMLRNVQP EDEGIYNCYI MNPPDRHRGH GKIHLQVLME EPPERDSTVA V IVGASVGG ...String: MHRDAWLPRP AFSLTGLSLF FSLVPPGRSM EVTVPATLNV LNGSDARLPC TFNSCYTVNH KQFSLNWTYQ ECNNCSEEMF LQFRMKIIN LKLERFQDRV EFSGNPSKYD VSVMLRNVQP EDEGIYNCYI MNPPDRHRGH GKIHLQVLME EPPERDSTVA V IVGASVGG FLAVVILVLM VVKCVRRKKE QKLSTDDLKT EEEGKTDGEG NPDDGAK |
-Macromolecule #2: Sodium channel protein type 9 subunit alpha
Macromolecule | Name: Sodium channel protein type 9 subunit alpha / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 231.211922 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMAMLPPP GPQSFVHFTK QSLALIEQRI AERKSKEPKE EKKDDDEEA PKPSSDLEAG KQLPFIYGDI PPGMVSEPLE DLDPYYADKK TFIVLNKGKT IFRFNATPAL YMLSPFSPLR R ISIKILVH ...String: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMAMLPPP GPQSFVHFTK QSLALIEQRI AERKSKEPKE EKKDDDEEA PKPSSDLEAG KQLPFIYGDI PPGMVSEPLE DLDPYYADKK TFIVLNKGKT IFRFNATPAL YMLSPFSPLR R ISIKILVH SLFSMLIMCT ILTNCIFMTM NNPPDWTKNV EYTFTGIYTF ESLVKILARG FCVGEFTFLR DPWNWLDFVV IV FAYLTEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLKHK CFR NSLENN ETLESIMNTL ESEEDFRKYF YYLEGSKDAL LCGFSTDSGQ CPEGYTCVKI GRNPDYGYTS FDTFSWAFLA LFRL MTQDY WENLYQQTLR AAGKTYMIFF VVVIFLGSFY LINLILAVVA MAYKEQNQAN IEEAKQKELE FQQMLDRLKK EQEEA EAIA AAAAEYTSIR RSRIMGLSES SSETSKLSSK SAKERRNRRK KKNQKKLSSG EEKGDAEKLS KSESEDSIRR KSFHLG VEG HRRAHEKRLS TPNQSPLSIR GSLFSARRSS RTSLFSFKGR GRDIGSETEF ADDEHSIFGD NESRRGSLFV PHRPQER RS SNISQASRSP PMLPVNGKMH SAVDCNGVVS LVDGRSALML PNGQLLPEVI IDKATSDDSG TTNQIHKKRR CSSYLLSE D MLNDPNLRQR AMSRASILTN TVEELEESRQ KCPPWWYRFA HKFLIWNCSP YWIKFKKCIY FIVMDPFVDL AITICIVLN TLFMAMEHHP MTEEFKNVLA IGNLVFTGIF AAEMVLKLIA MDPYEYFQVG WNIFDSLIVT LSLVELFLAD VEGLSVLRSF RLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII VFIFAVVGMQ LFGKSYKECV CKINDDCTLP RWHMNDFFHS F LIVFRVLC GEWIETMWDC MEVAGQAMCL IVYMMVMVIG NLVVLNLFLA LLLSSFSSDN LTAIEEDPDA NNLQIAVTRI KK GINYVKQ TLREFILKAF SKKPKISREI RQAEDLNTKK ENYISNHTLA EMSKGHNFLK EKDKISGFGS SVDKHLMEDS DGQ SFIHNP SLTVTVPIAP GESDLENMNA EELSSDSDSE YSKVRLNRSS SSECSTVDNP LPGEGEEAEA EPMNSDEPEA CFTD GCVWR FSCCQVNIES GKGKIWWNIR KTCYKIVEHS WFESFIVLMI LLSSGALAFE DIYIERKKTI KIILEYADKI FTYIF ILEM LLKWIAYGYK TYFTNAWCWL DFLIVDVSLV TLVANTLGYS DLGPIKSLRT LRALRPLRAL SRFEGMRVVV NALIGA IPS IMNVLLVCLI FWLIFSIMGV NLFAGKFYEC INTTDGSRFP ASQVPNRSEC FALMNVSQNV RWKNLKVNFD NVGLGYL SL LQVATFKGWT IIMYAAVDSV NVDKQPKYEY SLYMYIYFVV FIIFGSFFTL NLFIGVIIDN FNQQKKKLGG QDIFMTEE Q KKYYNAMKKL GSKKPQKPIP RPGNKIQGCI FDLVTNQAFD ISIMVLICLN MVTMMVEKEG QSQHMTEVLY WINVVFIIL FTGECVLKLI SLRHYYFTVG WNIFDFVVVI ISIVGMFLAD LIETYFVSPT LFRVIRLARI GRILRLVKGA KGIRTLLFAL MMSLPALFN IGLLLFLVMF IYAIFGMSNF AYVKKEDGIN DMFNFETFGN SMICLFQITT SAGWDGLLAP ILNSKPPDCD P KKVHPGSS VEGDCGNPSV GIFYFVSYII ISFLVVVNMY IAVILENFSV ATEESTEPLS EDDFEMFYEV WEKFDPDATQ FI EFSKLSD FAAALDPPLL IAKPNKVQLI AMDLPMVSGD RIHCLDILFA FTKRVLGESG EMDSLRSQME ERFMSANPSK VSY EPITTT LKRKQEDVSA TVIQRAYRRY RLRQNVKNIS SIYIKDGDRD DDLLNKKDMA FDNVNENSSP EKTDATSSTT SPPS YDSVT KPDKEKYEQD RTEKEDKGKD SKESKK |
-Macromolecule #3: Sodium channel subunit beta-1
Macromolecule | Name: Sodium channel subunit beta-1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.732115 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR QKGTEEFVKI LRYENEVLQL EEDERFEGR VVWNGSRGTK DLQDLSIFIT NVTYNHSGDY ECHVYRLLFF ENYEHNTSVV KKIHIEVVDK ANRDMASIVS E IMMYVLIV ...String: MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR QKGTEEFVKI LRYENEVLQL EEDERFEGR VVWNGSRGTK DLQDLSIFIT NVTYNHSGDY ECHVYRLLFF ENYEHNTSVV KKIHIEVVDK ANRDMASIVS E IMMYVLIV VLTIWLVAEM IYCYKKIAAA TETAAQENAS EYLAITSESK ENCTGVQVAE |
-Macromolecule #4: N-ACETYL-D-GLUCOSAMINE
Macromolecule | Name: N-ACETYL-D-GLUCOSAMINE / type: ligand / ID: 4 / Number of copies: 11 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
-Macromolecule #5: (1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-...
Macromolecule | Name: (1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.1~7,11~.0~1,6~]tetradec-3-ene-5,9,12,13,14-pentol (non-preferred name) type: ligand / ID: 5 / Number of copies: 1 / Formula: 9SR |
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Molecular weight | Theoretical: 319.268 Da |
Chemical component information | ![]() ChemComp-9SR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 263205 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |