[English] 日本語
Yorodumi
- EMDB-43663: Structure of full-length human cardiac sodium channel - Class-II. -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-43663
TitleStructure of full-length human cardiac sodium channel - Class-II.
Map dataStructure of full-length human cardiac sodium channel- Class-II
Sample
  • Organelle or cellular component: Sodium channel protein type 5 subunit alpha
    • Protein or peptide: Sodium channel protein type 5 subunit alpha
  • Ligand: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsVoltage gated sodium channel / Nav1.5 / Ion Transport / MEMBRANE PROTEIN
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 Purkinje myocyte action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / regulation of ventricular cardiac muscle cell membrane depolarization / AV node cell action potential / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential ...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 Purkinje myocyte action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / regulation of ventricular cardiac muscle cell membrane depolarization / AV node cell action potential / 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 / membrane depolarization during atrial cardiac muscle cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / cardiac ventricle development / brainstem development / membrane depolarization during AV node cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / positive regulation of action potential / membrane depolarization during bundle of His cell action potential / atrial cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / cardiac conduction system development / telencephalon development / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / positive regulation of sodium ion transport / regulation of sodium ion transmembrane transport / ventricular cardiac muscle cell action potential / regulation of ventricular cardiac muscle cell membrane repolarization / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of cardiac muscle cell contraction / Interaction between L1 and Ankyrins / ankyrin binding / voltage-gated sodium channel activity / sodium ion transport / nitric-oxide synthase binding / odontogenesis of dentin-containing tooth / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / fibroblast growth factor binding / intercalated disc / lateral plasma membrane / membrane depolarization / cardiac muscle contraction / T-tubule / regulation of heart rate / cellular response to calcium ion / cerebellum development / sodium ion transmembrane transport / positive regulation of epithelial cell proliferation / sarcolemma / caveola / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / protein domain specific binding / ubiquitin protein ligase binding / protein kinase binding / nucleolus / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / nucleoplasm / membrane / plasma membrane
Similarity search - Function
Voltage gated sodium channel, alpha-5 subunit / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Sodium ion transport-associated / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / SCN5A-like, C-terminal IQ motif / Voltage gated sodium channel, alpha subunit / Voltage-gated cation channel calcium and sodium / Voltage-dependent channel domain superfamily ...Voltage gated sodium channel, alpha-5 subunit / Voltage-gated Na+ ion channel, cytoplasmic domain / Cytoplasmic domain of voltage-gated Na+ ion channel / Sodium ion transport-associated / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / SCN5A-like, C-terminal IQ motif / Voltage gated sodium channel, alpha subunit / Voltage-gated cation channel calcium and sodium / Voltage-dependent channel domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Sodium channel protein type 5 subunit alpha
Similarity search - Component
Biological speciesMammalia (mammals) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsBiswas R / Chinthalapudi K
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)R01HL094450 United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Structural basis of human Na1.5 gating mechanisms.
Authors: Rupam Biswas / Ana Laura López-Serrano / Apoorva Purohit / Angelina Ramirez-Navarro / Hsiang-Ling Huang / Giovanna Grandinetti / Xiaolin Cheng / Sarah M Heissler / Isabelle Deschênes / Krishna Chinthalapudi /
Abstract: Voltage-gated Na1.5 channels are central to the generation and propagation of cardiac action potentials. Aberrations in their function are associated with a wide spectrum of cardiac diseases ...Voltage-gated Na1.5 channels are central to the generation and propagation of cardiac action potentials. Aberrations in their function are associated with a wide spectrum of cardiac diseases including arrhythmias and heart failure. Despite decades of progress in Na1.5 biology, the lack of structural insights into intracellular regions has hampered our understanding of its gating mechanisms. Here, we present two cryo-EM structures of human Na1.5 in open states, revealing sequential conformational changes in gating charges of the voltage-sensing domains (VSDs) and several intracellular regions. Despite the channel being in the open state, these structures show repositioning, but no dislodging of the IFM motif in the receptor site. Molecular dynamics analyses show our structures with CTD conduct Na ions. Notably, our structural findings highlight a dynamic C-terminal domain (CTD) and III-IV linker interaction, which regulates the conformation of VSDs and pore opening. Electrophysiological studies confirm that disrupting this interaction alters fast inactivation of Na1.5. Together, our structure-function studies establish a foundation for understanding the gating mechanisms of Na1.5 and the mechanisms underlying CTD-related channelopathies.
History
DepositionFeb 8, 2024-
Header (metadata) releaseFeb 12, 2025-
Map releaseFeb 12, 2025-
UpdateFeb 25, 2026-
Current statusFeb 25, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_43663.png

Downloads & links

-
Map

FileDownload / File: emd_43663.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationStructure of full-length human cardiac sodium channel- Class-II
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.9 Å/pix.
x 256 pix.
= 230.144 Å		0.9 Å/pix.
x 256 pix.
= 230.144 Å		0.9 Å/pix.
x 256 pix.
= 230.144 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.899 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 2.5
Minimum - Maximum-19.725577999999999 - 30.051494999999999
Average (Standard dev.)-0.000000000003345 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 230.144 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_43663_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half Map B

Fileemd_43663_half_map_1.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half Map A

Fileemd_43663_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Sodium channel protein type 5 subunit alpha

EntireName: Sodium channel protein type 5 subunit alpha
Components
  • Organelle or cellular component: Sodium channel protein type 5 subunit alpha
    • Protein or peptide: Sodium channel protein type 5 subunit alpha
  • Ligand: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: Sodium channel protein type 5 subunit alpha

SupramoleculeName: Sodium channel protein type 5 subunit alpha / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: Full-length protein
Source (natural)Organism: Mammalia (mammals)
Molecular weightTheoretical: 226.9 KDa

-
Macromolecule #1: Sodium channel protein type 5 subunit alpha

MacromoleculeName: Sodium channel protein type 5 subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 227.152156 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSTTLQ ESREGLPEEE APRPQLDLQA SKKLPDLYGN PPQELIGEPL EDLDPFYST QKTFIVLNKG KTIFRFSATN ALYVLSPFHP IRRAAVKILV HSLFNMLIMC TILTNCVFMA QHDPPPWTKY V EYTFTAIY ...String:
MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSTTLQ ESREGLPEEE APRPQLDLQA SKKLPDLYGN PPQELIGEPL EDLDPFYST QKTFIVLNKG KTIFRFSATN ALYVLSPFHP IRRAAVKILV HSLFNMLIMC TILTNCVFMA QHDPPPWTKY V EYTFTAIY TFESLVKILA RGFCLHAFTF LRDPWNWLDF SVIIMAYTTE FVDLGNVSAL RTFRVLRALK TISVISGLKT IV GALIQSV KKLADVMVLT VFCLSVFALI GLQLFMGNLR HKCVRNFTAL NGTNGSVEAD GLVWESLDLY LSDPENYLLK NGT SDVLLC GNSSDAGTCP EGYRCLKAGE NPDHGYTSFD SFAWAFLALF RLMTQDCWER LYQQTLRSAG KIYMIFFMLV IFLG SFYLV NLILAVVAMA YEEQNQATIA ETEEKEKRFQ EAMEMLKKEH EALTIRGVDT VSRSSLEMSP LAPVNSHERR SKRRK RMSS GTEECGEDRL PKSDSEDGPR AMNHLSLTRG LSRTSMKPRS SRGSIFTFRR RDLGSEADFA DDENSTAGES ESHHTS LLV PWPLRRTSAQ GQPSPGTSAP GHALHGKKNS TVDCNGVVSL LGAGDPEATS PGSHLLRPVM LEHPPDTTTP SEEPGGP QM LTSQAPCVDG FEEPGARQRA LSAVSVLTSA LEELEESRHK CPPCWNRLAQ RYLIWECCPL WMSIKQGVKL VVMDPFTD L TITMCIVLNT LFMALEHYNM TSEFEEMLQV GNLVFTGIFT AEMTFKIIAL DPYYYFQQGW NIFDSIIVIL SLMELGLSR MSNLSVLRSF RLLRVFKLAK SWPTLNTLIK IIGNSVGALG NLTLVLAIIV FIFAVVGMQL FGKNYSELRD SDSGLLPRWH MMDFFHAFL IIFRILCGEW IETMWDCMEV SGQSLCLLVF LLVMVIGNLV VLNLFLALLL SSFSADNLTA PDEDREMNNL Q LALARIQR GLRFVKRTTW DFCCGLLRQR PQKPAALAAQ GQLPSCIATP YSPPPPETEK VPPTRKETRF EEGEQPGQGT PG DPEPVCV PIAVAESDTD DQEEDEENSL GTEEESSKQQ ESQPVSGGPE APPDSRTWSQ VSATASSEAE ASASQADWRQ QWK AEPQAP GCGETPEDSC SEGSTADMTN TAELLEQIPD LGQDVKDPED CFTEGCVRRC PCCAVDTTQA PGKVWWRLRK TCYH IVEHS WFETFIIFMI LLSSGALAFE DIYLEERKTI KVLLEYADKM FTYVFVLEML LKWVAYGFKK YFTNAWCWLD FLIVD VSLV SLVANTLGFA EMGPIKSLRT LRALRPLRAL SRFEGMRVVV NALVGAIPSI MNVLLVCLIF WLIFSIMGVN LFAGKF GRC INQTEGDLPL NYTIVNNKSQ CESLNLTGEL YWTKVKVNFD NVGAGYLALL QVATFKGWMD IMYAAVDSRG YEEQPQW EY NLYMYIYFVI FIIFGSFFTL NLFIGVIIDN FNQQKKKLGG QDIFMTEEQK KYYNAMKKLG SKKPQKPIPR PLNKYQGF I FDIVTKQAFD VTIMFLICLN MVTMMVETDD QSPEKINILA KINLLFVAIF TGECIVKLAA LRHYYFTNSW NIFDFVVVI LSIVGTVLSD IIQKYFFSPT LFRVIRLARI GRILRLIRGA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI YSIFGMANFA YVKWEAGID DMFNFQTFAN SMLCLFQITT SAGWDGLLSP ILNTGPPYCD PTLPNSNGSR GDCGSPAVGI LFFTTYIIIS F LIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW EKFDPEATQF IEYSVLSDFA DALSEPLRIA KPNQISLINM DL PMVSGDR IHCMDILFAF TKRVLGESGE MDALKIQMEE KFMAANPSKI SYEPITTTLR RKHEEVSAMV IQRAFRRHLL QRS LKHASF LFRQQAGSGL SEEDAPEREG LIAYVMSENF SRPLGPPSSS SISSTSFPPS YDSVTRATSD NLQVRGSDYS HSED LADFP PSPDRDRESI V

UniProtKB: Sodium channel protein type 5 subunit alpha

-
Macromolecule #4: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyl...

MacromoleculeName: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate
type: ligand / ID: 4 / Number of copies: 2 / Formula: 6OU
Molecular weightTheoretical: 717.996 Da
Chemical component information

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

-
Macromolecule #5: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 5 / Number of copies: 7 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

-
Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 65347
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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