[English] 日本語
Yorodumi
- EMDB-34388: Cryo-EM structure of human NaV1.6/beta1/beta2-4,9-anhydro-tetrodotoxin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-34388
TitleCryo-EM structure of human NaV1.6/beta1/beta2-4,9-anhydro-tetrodotoxin
Map data
Sample
  • Complex: Structure of human voltage-gated sodium channel Nav1.6 in complex with auxiliary beta subunits
    • Protein or peptide: Sodium channel subunit beta-1
    • Protein or peptide: Sodium channel protein type 8 subunit alpha
    • Protein or peptide: Sodium channel subunit beta-2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: (1R,2S,3S,4R,5R,9S,11S,12S,14R)-7-amino-2,4,12-trihydroxy-2-(hydroxymethyl)-10,13,15-trioxa-6,8-diazapentacyclo[7.4.1.1~3,12~.0~5,11~.0~5,14~]pentadec-7-en-8-ium (non-preferred name)
Function / homology
Function and homology information


corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / axon initial segment / sodium ion binding ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / membrane depolarization during Purkinje myocyte cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / axon initial segment / sodium ion binding / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / voltage-gated sodium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / peripheral nervous system development / node of Ranvier / cardiac muscle cell action potential involved in contraction / high voltage-gated calcium channel activity / locomotion / optic nerve development / voltage-gated sodium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / sodium channel inhibitor activity / neuronal action potential propagation / Interaction between L1 and Ankyrins / parallel fiber to Purkinje cell synapse / sodium ion transport / voltage-gated calcium channel complex / regulation of heart rate by cardiac conduction / Phase 0 - rapid depolarisation / calcium ion import across plasma membrane / membrane depolarization / neuronal action potential / sodium ion transmembrane transport / sodium channel regulator activity / intercalated disc / presynaptic active zone membrane / cardiac muscle contraction / T-tubule / myelination / axon guidance / postsynaptic density membrane / positive regulation of neuron projection development / Sensory perception of sweet, bitter, and umami (glutamate) taste / Z disc / cell junction / gene expression / nervous system development / response to heat / perikaryon / chemical synaptic transmission / cytoplasmic vesicle / transmembrane transporter binding / cell adhesion / axon / glutamatergic synapse / synapse / extracellular region / ATP binding / membrane / plasma membrane
Similarity search - Function
Voltage gated sodium channel, alpha-8 subunit / Sodium channel subunit beta-1/beta-3 / Myelin P0 protein-related / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / Sodium ion transport-associated / Voltage gated sodium channel, alpha subunit / IQ calmodulin-binding motif ...Voltage gated sodium channel, alpha-8 subunit / Sodium channel subunit beta-1/beta-3 / Myelin P0 protein-related / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / Sodium ion transport-associated / Voltage gated sodium channel, alpha subunit / IQ calmodulin-binding motif / Voltage-gated cation channel calcium and sodium / Short calmodulin-binding motif containing conserved Ile and Gln residues. / IQ motif profile. / IQ motif, EF-hand binding site / Voltage-dependent channel domain superfamily / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Ion transport domain / Ion transport protein / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Sodium channel subunit beta-2 / Sodium channel subunit beta-1 / Sodium channel protein type 8 subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsLi Y / Jiang D
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32271272 China
CitationJournal: Nat Commun / Year: 2023
Title: Structure of human Na1.6 channel reveals Na selectivity and pore blockade by 4,9-anhydro-tetrodotoxin.
Authors: Yue Li / Tian Yuan / Bo Huang / Feng Zhou / Chao Peng / Xiaojing Li / Yunlong Qiu / Bei Yang / Yan Zhao / Zhuo Huang / Daohua Jiang /
Abstract: The sodium channel Na1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of Na1.6 has been ...The sodium channel Na1.6 is widely expressed in neurons of the central and peripheral nervous systems, which plays a critical role in regulating neuronal excitability. Dysfunction of Na1.6 has been linked to epileptic encephalopathy, intellectual disability and movement disorders. Here we present cryo-EM structures of human Na1.6/β1/β2 alone and complexed with a guanidinium neurotoxin 4,9-anhydro-tetrodotoxin (4,9-ah-TTX), revealing molecular mechanism of Na1.6 inhibition by the blocker. The apo-form structure reveals two potential Na binding sites within the selectivity filter, suggesting a possible mechanism for Na selectivity and conductance. In the 4,9-ah-TTX bound structure, 4,9-ah-TTX binds to a pocket similar to the tetrodotoxin (TTX) binding site, which occupies the Na binding sites and completely blocks the channel. Molecular dynamics simulation results show that subtle conformational differences in the selectivity filter affect the affinity of TTX analogues. Taken together, our results provide important insights into Na1.6 structure, ion conductance, and inhibition.
History
DepositionSep 24, 2022-
Header (metadata) releaseMar 8, 2023-
Map releaseMar 8, 2023-
UpdateMar 8, 2023-
Current statusMar 8, 2023Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_34388.png

Downloads & links

-
Map

FileDownload / File: emd_34388.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.04 Å
Density
Contour LevelBy AUTHOR: 0.4
Minimum - Maximum-1.8746638 - 3.2081673
Average (Standard dev.)0.006212063 (±0.07596081)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 266.24 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_34388_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_34388_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Structure of human voltage-gated sodium channel Nav1.6 in complex...

EntireName: Structure of human voltage-gated sodium channel Nav1.6 in complex with auxiliary beta subunits
Components
  • Complex: Structure of human voltage-gated sodium channel Nav1.6 in complex with auxiliary beta subunits
    • Protein or peptide: Sodium channel subunit beta-1
    • Protein or peptide: Sodium channel protein type 8 subunit alpha
    • Protein or peptide: Sodium channel subunit beta-2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: (1R,2S,3S,4R,5R,9S,11S,12S,14R)-7-amino-2,4,12-trihydroxy-2-(hydroxymethyl)-10,13,15-trioxa-6,8-diazapentacyclo[7.4.1.1~3,12~.0~5,11~.0~5,14~]pentadec-7-en-8-ium (non-preferred name)

-
Supramolecule #1: Structure of human voltage-gated sodium channel Nav1.6 in complex...

SupramoleculeName: Structure of human voltage-gated sodium channel Nav1.6 in complex with auxiliary beta subunits
type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Sodium channel subunit beta-1

MacromoleculeName: Sodium channel subunit beta-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.732115 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 #2: Sodium channel protein type 8 subunit alpha

MacromoleculeName: Sodium channel protein type 8 subunit alpha / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 225.520609 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE AGKSLPFIYG DIPQGLVAVP LEDFDPYYL TQKTFVVLNR GKTLFRFSAT PALYILSPFN LIRRIAIKIL IHSVFSMIIM CTILTNCVFM TFSNPPDWSK N VEYTFTGI ...String:
MAARLLAPPG PDSFKPFTPE SLANIERRIA ESKLKKPPKA DGSHREDDED SKPKPNSDLE AGKSLPFIYG DIPQGLVAVP LEDFDPYYL TQKTFVVLNR GKTLFRFSAT PALYILSPFN LIRRIAIKIL IHSVFSMIIM CTILTNCVFM TFSNPPDWSK N VEYTFTGI YTFESLVKII ARGFCIDGFT FLRDPWNWLD FSVIMMAYIT EFVNLGNVSA LRTFRVLRAL KTISVIPGLK TI VGALIQS VKKLSDVMIL TVFCLSVFAL IGLQLFMGNL RNKCVVWPIN FNESYLENGT KGFDWEEYIN NKTNFYTVPG MLE PLLCGN SSDAGQCPEG YQCMKAGRNP NYGYTSFDTF SWAFLALFRL MTQDYWENLY QLTLRAAGKT YMIFFVLVIF VGSF YLVNL ILAVVAMAYE EQNQATLEEA EQKEAEFKAM LEQLKKQQEE AQAAAMATSA GTVSEDAIEE EGEEGGGSPR SSSEI SKLS SKSAKERRNR RKKRKQKELS EGEEKGDPEK VFKSESEDGM RRKAFRLPDN RIGRKFSIMN QSLLSIPGSP FLSRHN SKS SIFSFRGPGR FRDPGSENEF ADDEHSTVEE SEGRRDSLFI PIRARERRSS YSGYSGYSQG SRSSRIFPSL RRSVKRN ST VDCNGVVSLI GGPGSHIGGR LLPEATTEVE IKKKGPGSLL VSMDQLASYG RKDRINSIMS VVTNTLVEEL EESQRKCP P CWYKFANTFL IWECHPYWIK LKEIVNLIVM DPFVDLAITI CIVLNTLFMA MEHHPMTPQF EHVLAVGNLV FTGIFTAEM FLKLIAMDPY YYFQEGWNIF DGFIVSLSLM ELSLADVEGL SVLRSFRLLR VFKLAKSWPT LNMLIKIIGN SVGALGNLTL VLAIIVFIF AVVGMQLFGK SYKECVCKIN QDCELPRWHM HDFFHSFLIV FRVLCGEWIE TMWDCMEVAG QAMCLIVFMM V MVIGNLVV LNLFLALLLS SFSADNLAAT DDDGEMNNLQ ISVIRIKKGV AWTKLKVHAF MQAHFKQREA DEVKPLDELY EK KANCIAN HTGADIHRNG DFQKNGNGTT SGIGSSVEKY IIDEDHMSFI NNPNLTVRVP IAVGESDFEN LNTEDVSSES DPE GSKDKL DDTSSSEGST IDIKPEVEEV PVEQPEEYLD PDACFTEGCV QRFKCCQVNI EEGLGKSWWI LRKTCFLIVE HNWF ETFII FMILLSSGAL AFEDIYIEQR KTIRTILEYA DKVFTYIFIL EMLLKWTAYG FVKFFTNAWC WLDFLIVAVS LVSLI ANAL GYSELGAIKS LRTLRALRPL RALSRFEGMR VVVNALVGAI PSIMNVLLVC LIFWLIFSIM GVNLFAGKYH YCFNET SEI RFEIEDVNNK TECEKLMEGN NTEIRWKNVK INFDNVGAGY LALLQVATFK GWMDIMYAAV DSRKPDEQPK YEDNIYM YI YFVIFIIFGS FFTLNLFIGV IIDNFNQQKK KFGGQDIFMT EEQKKYYNAM KKLGSKKPQK PIPRPLNKIQ GIVFDFVT Q QAFDIVIMML ICLNMVTMMV ETDTQSKQME NILYWINLVF VIFFTCECVL KMFALRHYYF TIGWNIFDFV VVILSIVGM FLADIIEKYF VSPTLFRVIR LARIGRILRL IKGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIFSIFGM SNFAYVKHEA GIDDMFNFE TFGNSMICLF QITTSAGWDG LLLPILNRPP DCSLDKEHPG SGFKGDCGNP SVGIFFFVSY IIISFLIVVN M YIAIILEN FSVATEESAD PLSEDDFETF YEIWEKFDPD ATQFIEYCKL ADFADALEHP LRVPKPNTIE LIAMDLPMVS GD RIHCLDI LFAFTKRVLG DSGELDILRQ QMEERFVASN PSKVSYEPIT TTLRRKQEEV SAVVLQRAYR GHLARRGFIC KKT TSNKLE NGGTHREKKE STPSTASLPS YDSVTKPEKE KQQRAEEGRR ERAKRQKEVR ESKC

-
Macromolecule #3: Sodium channel subunit beta-2

MacromoleculeName: Sodium channel subunit beta-2 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.355859 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

-
Macromolecule #6: (1R,2S,3S,4R,5R,9S,11S,12S,14R)-7-amino-2,4,12-trihydroxy-2-(hydr...

MacromoleculeName: (1R,2S,3S,4R,5R,9S,11S,12S,14R)-7-amino-2,4,12-trihydroxy-2-(hydroxymethyl)-10,13,15-trioxa-6,8-diazapentacyclo[7.4.1.1~3,12~.0~5,11~.0~5,14~]pentadec-7-en-8-ium (non-preferred name)
type: ligand / ID: 6 / Number of copies: 1 / Formula: WMK
Molecular weightTheoretical: 301.253 Da
Chemical component information

ChemComp-WMK:
(1R,2S,3S,4R,5R,9S,11S,12S,14R)-7-amino-2,4,12-trihydroxy-2-(hydroxymethyl)-10,13,15-trioxa-6,8-diazapentacyclo[7.4.1.1~3,12~.0~5,11~.0~5,14~]pentadec-7-en-8-ium (non-preferred name)

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 9.2 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6j8i

Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 76448

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more