[English] 日本語
Yorodumi
- EMDB-30850: voltage-gated sodium channel Nav1.5-E1784K -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-30850
Titlevoltage-gated sodium channel Nav1.5-E1784K
Map dataCryo-EM map of voltage-gated sodium channel
Sample
  • Complex: voltage-gated sodium channelSodium channel
    • Protein or peptide: Sodium channel protein type 5 subunit alpha
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
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 / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / cardiac ventricle development / 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 / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / cardiac ventricle development / response to denervation involved in regulation of muscle adaptation / 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 / cardiac conduction system development / regulation of atrial cardiac muscle cell membrane depolarization / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / ventricular cardiac muscle cell action potential / membrane depolarization during action potential / cardiac muscle cell action potential involved in contraction / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / ankyrin binding / sodium ion transport / fibroblast growth factor binding / nitric-oxide synthase binding / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / lateral plasma membrane / sodium ion transmembrane transport / neuronal action potential / cardiac muscle contraction / T-tubule / cellular response to calcium ion / regulation of heart rate / cerebellum development / caveola / positive regulation of epithelial cell proliferation / sarcolemma / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / protein domain specific binding / axon / ubiquitin protein ligase binding / nucleolus / protein kinase binding / 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 / Voltage-gated sodium channel alpha subunit, inactivation gate / Sodium ion transport-associated / Sodium ion transport-associated / 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 speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsYan N / Pan X / Li Z
Funding support China, 1 items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2016YFA0500402 China
CitationJournal: Proc Natl Acad Sci U S A / Year: 2021
Title: Structure of human Na1.5 reveals the fast inactivation-related segments as a mutational hotspot for the long QT syndrome.
Authors: Zhangqiang Li / Xueqin Jin / Tong Wu / Xin Zhao / Weipeng Wang / Jianlin Lei / Xiaojing Pan / Nieng Yan /
Abstract: Na1.5 is the primary voltage-gated Na (Na) channel in the heart. Mutations of Na1.5 are associated with various cardiac disorders exemplified by the type 3 long QT syndrome (LQT3) and Brugada ...Na1.5 is the primary voltage-gated Na (Na) channel in the heart. Mutations of Na1.5 are associated with various cardiac disorders exemplified by the type 3 long QT syndrome (LQT3) and Brugada syndrome (BrS). E1784K is a common mutation that has been found in both LQT3 and BrS patients. Here we present the cryo-EM structure of the human Na1.5-E1784K variant at an overall resolution of 3.3 Å. The structure is nearly identical to that of the wild-type human Na1.5 bound to quinidine. Structural mapping of 91- and 178-point mutations that are respectively associated with LQT3 and BrS reveals a unique distribution pattern for LQT3 mutations. Whereas the BrS mutations spread evenly on the structure, LQT3 mutations are clustered mainly to the segments in repeats III and IV that are involved in gating, voltage-sensing, and particularly inactivation. A mutational hotspot involving the fast inactivation segments is identified and can be mechanistically interpreted by our "door wedge" model for fast inactivation. The structural analysis presented here, with a focus on the impact of mutations on inactivation and late sodium current, establishes a structure-function relationship for the mechanistic understanding of Na1.5 channelopathies.
History
DepositionJan 4, 2021-
Header (metadata) releaseMar 24, 2021-
Map releaseMar 24, 2021-
UpdateMar 24, 2021-
Current statusMar 24, 2021Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7dtc
  • Surface level: 0.4
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-7dtc
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_30850.png

Downloads & links

-
Map

FileDownload / File: emd_30850.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM map of voltage-gated sodium channel
Voxel sizeX=Y=Z: 1.0825 Å
Density
Contour LevelBy AUTHOR: 0.26 / Movie #1: 0.4
Minimum - Maximum-0.6931059 - 1.4888437
Average (Standard dev.)0.01001106 (±0.061956596)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 259.8 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.08251.08251.0825
M x/y/z240240240
origin x/y/z0.0000.0000.000
length x/y/z259.800259.800259.800
α/β/γ90.00090.00090.000
start NX/NY/NZ1219875
NX/NY/NZ141223232
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS240240240
D min/max/mean-0.6931.4890.010

-
Supplemental data

-
Sample components

-
Entire : voltage-gated sodium channel

EntireName: voltage-gated sodium channelSodium channel
Components
  • Complex: voltage-gated sodium channelSodium channel
    • Protein or peptide: Sodium channel protein type 5 subunit alpha
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

-
Supramolecule #1: voltage-gated sodium channel

SupramoleculeName: voltage-gated sodium channel / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

-
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: 231.744 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMANFLLP RGTSSFRRFT RESLAAIEKR MAEKQARGST TLQESREGL PEEEAPRPQL DLQASKKLPD LYGNPPQELI GEPLEDLDPF YSTQKTFIVL NKGKTIFRFS ATNALYVLSP F HPIRRAAV ...String:
MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMANFLLP RGTSSFRRFT RESLAAIEKR MAEKQARGST TLQESREGL PEEEAPRPQL DLQASKKLPD LYGNPPQELI GEPLEDLDPF YSTQKTFIVL NKGKTIFRFS ATNALYVLSP F HPIRRAAV KILVHSLFNM LIMCTILTNC VFMAQHDPPP WTKYVEYTFT AIYTFESLVK ILARGFCLHA FTFLRDPWNW LD FSVIIMA YTTEFVDLGN VSALRTFRVL RALKTISVIS GLKTIVGALI QSVKKLADVM VLTVFCLSVF ALIGLQLFMG NLR HKCVRN FTALNGTNGS VEADGLVWES LDLYLSDPEN YLLKNGTSDV LLCGNSSDAG TCPEGYRCLK AGENPDHGYT SFDS FAWAF LALFRLMTQD CWERLYQQTL RSAGKIYMIF FMLVIFLGSF YLVNLILAVV AMAYEEQNQA TIAETEEKEK RFQEA MEML KKEHEALTIR GVDTVSRSSL EMSPLAPVNS HERRSKRRKR MSSGTEECGE DRLPKSDSED GPRAMNHLSL TRGLSR TSM KPRSSRGSIF TFRRRDLGSE ADFADDENST AGESESHHTS LLVPWPLRRT SAQGQPSPGT SAPGHALHGK KNSTVDC NG VVSLLGAGDP EATSPGSHLL RPVMLEHPPD TTTPSEEPGG PQMLTSQAPC VDGFEEPGAR QRALSAVSVL TSALEELE E SRHKCPPCWN RLAQRYLIWE CCPLWMSIKQ GVKLVVMDPF TDLTITMCIV LNTLFMALEH YNMTSEFEEM LQVGNLVFT GIFTAEMTFK IIALDPYYYF QQGWNIFDSI IVILSLMELG LSRMSNLSVL RSFRLLRVFK LAKSWPTLNT LIKIIGNSVG ALGNLTLVL AIIVFIFAVV GMQLFGKNYS ELRDSDSGLL PRWHMMDFFH AFLIIFRILC GEWIETMWDC MEVSGQSLCL L VFLLVMVI GNLVVLNLFL ALLLSSFSAD NLTAPDEDRE MNNLQLALAR IQRGLRFVKR TTWDFCCGLL RQRPQKPAAL AA QGQLPSC IATPYSPPPP ETEKVPPTRK ETRFEEGEQP GQGTPGDPEP VCVPIAVAES DTDDQEEDEE NSLGTEEESS KQQ ESQPVS GGPEAPPDSR TWSQVSATAS SEAEASASQA DWRQQWKAEP QAPGCGETPE DSCSEGSTAD MTNTAELLEQ IPDL GQDVK DPEDCFTEGC VRRCPCCAVD TTQAPGKVWW RLRKTCYHIV EHSWFETFII FMILLSSGAL AFEDIYLEER KTIKV LLEY ADKMFTYVFV LEMLLKWVAY GFKKYFTNAW CWLDFLIVDV SLVSLVANTL GFAEMGPIKS LRTLRALRPL RALSRF EGM RVVVNALVGA IPSIMNVLLV CLIFWLIFSI MGVNLFAGKF GRCINQTEGD LPLNYTIVNN KSQCESLNLT GELYWTK VK VNFDNVGAGY LALLQVATFK GWMDIMYAAV DSRGYEEQPQ WEYNLYMYIY FVIFIIFGSF FTLNLFIGVI IDNFNQQK K KLGGQDIFMT EEQKKYYNAM KKLGSKKPQK PIPRPLNKYQ GFIFDIVTKQ AFDVTIMFLI CLNMVTMMVE TDDQSPEKI NILAKINLLF VAIFTGECIV KLAALRHYYF TNSWNIFDFV VVILSIVGTV LSDIIQKYFF SPTLFRVIRL ARIGRILRLI RGAKGIRTL LFALMMSLPA LFNIGLLLFL VMFIYSIFGM ANFAYVKWEA GIDDMFNFQT FANSMLCLFQ ITTSAGWDGL L SPILNTGP PYCDPTLPNS NGSRGDCGSP AVGILFFTTY IIISFLIVVN MYIAIILENF SVATEESTKP LSEDDFDMFY EI WEKFDPE ATQFIEYSVL SDFADALSEP LRIAKPNQIS LINMDLPMVS GDRIHCMDIL FAFTKRVLGE SGEMDALKIQ MEE KFMAAN PSKISYEPIT TTLRRKHEEV SAMVIQRAFR RHLLQRSLKH ASFLFRQQAG SGLSEEDAPE REGLIAYVMS ENFS RPLGP PSSSSISSTS FPPSYDSVTR ATSDNLQVRG SDYSHSEDLA DFPPSPDRDR ESIV

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

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

-
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
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 24.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 147600

+
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