[English] 日本語
Yorodumi
- PDB-7dtd: Voltage-gated sodium channel Nav1.1 and beta4 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7dtd
TitleVoltage-gated sodium channel Nav1.1 and beta4
Components
  • Sodium channel protein type 1 subunit alpha
  • Sodium channel subunit beta-4
KeywordsMEMBRANE PROTEIN / Voltage-gated sodium channel
Function / homology
Function and homology information


AV node cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / cardiac muscle cell action potential involved in contraction / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / positive regulation of sodium ion transport / voltage-gated sodium channel activity ...AV node cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / cardiac muscle cell action potential involved in contraction / membrane depolarization during cardiac muscle cell action potential / membrane depolarization during action potential / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / positive regulation of sodium ion transport / voltage-gated sodium channel activity / neuronal action potential / sodium ion transport / regulation of heart rate by cardiac conduction / voltage-gated ion channel activity / intrinsic component of plasma membrane / sodium ion transmembrane transport / intercalated disc / cardiac muscle contraction / sodium channel regulator activity / regulation of ion transmembrane transport / cation channel activity / detection of mechanical stimulus involved in sensory perception of pain / Z disc / ion channel binding / nuclear body / axon / nucleoplasm / plasma membrane
Voltage gated sodium channel, alpha-1 subunit / Voltage-gated cation channel calcium and sodium / Immunoglobulin-like domain superfamily / Voltage-dependent channel domain superfamily / Voltage-gated Na+ ion channel, cytoplasmic domain / Immunoglobulin-like fold / Immunoglobulin V-set domain / Sodium ion transport-associated / Immunoglobulin-like domain / Ion transport domain ...Voltage gated sodium channel, alpha-1 subunit / Voltage-gated cation channel calcium and sodium / Immunoglobulin-like domain superfamily / Voltage-dependent channel domain superfamily / Voltage-gated Na+ ion channel, cytoplasmic domain / Immunoglobulin-like fold / Immunoglobulin V-set domain / Sodium ion transport-associated / Immunoglobulin-like domain / Ion transport domain / Immunoglobulin subtype / Voltage gated sodium channel, alpha subunit / Myelin P0 protein-related
Sodium channel protein type 1 subunit alpha / Sodium channel subunit beta-4
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsYan, N. / Pan, X. / Li, Z. / Huang, G.
Funding support China, 1items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2016YFA0500402 China
CitationJournal: 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.
Validation Report
SummaryFull reportAbout validation report
History
DepositionJan 4, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 7, 2021Provider: repository / Type: Initial release

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-30851
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Sodium channel subunit beta-4
A: Sodium channel protein type 1 subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)260,2277
Polymers258,7972
Non-polymers1,4305
Water0
1


TypeNameSymmetry operationNumber
identity operation1_5551
Buried area1330 Å2
ΔGint6 kcal/mol
Surface area66800 Å2

-
Components

#1: Protein Sodium channel subunit beta-4 /


Mass: 25000.980 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SCN4B / Production host: Homo sapiens (human) / References: UniProt: Q8IWT1
#2: Protein Sodium channel protein type 1 subunit alpha / / Sodium channel protein brain I subunit alpha / Sodium channel protein type I subunit alpha / ...Sodium channel protein brain I subunit alpha / Sodium channel protein type I subunit alpha / Voltage-gated sodium channel subunit alpha Nav1.1


Mass: 233796.141 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SCN1A, NAC1, SCN1 / Production host: Homo sapiens (human) / References: UniProt: P35498
#3: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#4: Chemical ChemComp-9Z9 / (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en


Mass: 544.805 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H56O5 / Comment: detergent*YM
Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Voltage-gated sodium channelSodium channel / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 48 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 133127 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Aug 12, 2020. New: Covid-19 info

New: Covid-19 info

  • 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. New: 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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

Read more

-
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.

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