[English] 日本語
Yorodumi
- EMDB-18716: TDP-43 amyloid fibrils: Morphology-1b -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-18716
TitleTDP-43 amyloid fibrils: Morphology-1b
Map data
Sample
  • Complex: TDP-43 amyloid fibrils: Morphology-1b
    • Protein or peptide: TAR DNA-binding protein 43
KeywordsAmyloidosis / Protein misfolding disease / Amyloid fibrils / Cryo electron microscopy / Amyloid key / PROTEIN FIBRIL
Function / homology
Function and homology information


nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular membraneless organelle / negative regulation by host of viral transcription / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing ...nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular membraneless organelle / negative regulation by host of viral transcription / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing / negative regulation of protein phosphorylation / mRNA 3'-UTR binding / molecular condensate scaffold activity / regulation of circadian rhythm / regulation of protein stability / positive regulation of insulin secretion / positive regulation of protein import into nucleus / cytoplasmic stress granule / mRNA processing / rhythmic process / double-stranded DNA binding / regulation of gene expression / regulation of apoptotic process / amyloid fibril formation / regulation of cell cycle / nuclear speck / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of gene expression / lipid binding / chromatin / mitochondrion / DNA binding / RNA binding / nucleoplasm / identical protein binding / nucleus
Similarity search - Function
TAR DNA-binding protein 43, N-terminal / : / TAR DNA-binding protein 43, N-terminal domain / TAR DNA-binding protein 43, C-terminal / RNA recognition motif / RNA recognition motif / Eukaryotic RNA Recognition Motif (RRM) profile. / RNA recognition motif domain / RNA-binding domain superfamily / Nucleotide-binding alpha-beta plait domain superfamily
Similarity search - Domain/homology
TAR DNA-binding protein 43
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 4.05 Å
AuthorsSharma K / Shenoy J / Loquet A / Schmidt M / Faendrich M
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2024
Title: Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils.
Authors: Kartikay Sharma / Fabian Stockert / Jayakrishna Shenoy / Mélanie Berbon / Muhammed Bilal Abdul-Shukkoor / Birgit Habenstein / Antoine Loquet / Matthias Schmidt / Marcus Fändrich /
Abstract: The transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, ...The transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, abnormal aggregation of TDP-43 has been linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration through the aggregation of its C-terminal domain. Here, we report a cryo-electron microscopy (cryo-EM)-based structural characterization of TDP-43 fibrils obtained from the full-length protein. We find that the fibrils are polymorphic and contain three different amyloid structures. The structures differ in the number and relative orientation of the protofilaments, although they share a similar fold containing an amyloid key motif. The observed fibril structures differ from previously described conformations of TDP-43 fibrils and help to better understand the structural landscape of the amyloid fibril structures derived from this protein.
History
DepositionOct 24, 2023-
Header (metadata) releaseJan 24, 2024-
Map releaseJan 24, 2024-
UpdateJan 24, 2024-
Current statusJan 24, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_18716.png

Downloads & links

-
Map

FileDownload / File: emd_18716.map.gz / Format: CCP4 / Size: 46.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 230 pix.
= 239.2 Å		1.04 Å/pix.
x 230 pix.
= 239.2 Å		1.04 Å/pix.
x 230 pix.
= 239.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.04 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.014
Minimum - Maximum-0.044180445 - 0.06534384
Average (Standard dev.)0.00017026447 (±0.002012369)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions230230230
Spacing230230230
CellA=B=C: 239.2 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_18716_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_18716_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : TDP-43 amyloid fibrils: Morphology-1b

EntireName: TDP-43 amyloid fibrils: Morphology-1b
Components
  • Complex: TDP-43 amyloid fibrils: Morphology-1b
    • Protein or peptide: TAR DNA-binding protein 43

-
Supramolecule #1: TDP-43 amyloid fibrils: Morphology-1b

SupramoleculeName: TDP-43 amyloid fibrils: Morphology-1b / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: In vitro formed TDP-43 amyloid fibrils
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: TAR DNA-binding protein 43

MacromoleculeName: TAR DNA-binding protein 43 / type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 44.784742 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MSEYIRVTED ENDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI LHAPDAGWGN LVYVVNYPKD NKRKMDETD ASSAVKVKRA VQKTSDLIVL GLPWKTTEQD LKEYFSTFGE VLMVQVKKDL KTGHSKGFGF VRFTEYETQV K VMSQRHMI ...String:
MSEYIRVTED ENDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI LHAPDAGWGN LVYVVNYPKD NKRKMDETD ASSAVKVKRA VQKTSDLIVL GLPWKTTEQD LKEYFSTFGE VLMVQVKKDL KTGHSKGFGF VRFTEYETQV K VMSQRHMI DGRWCDCKLP NSKQSQDEPL RSRKVFVGRC TEDMTEDELR EFFSQYGDVM DVFIPKPFRA FAFVTFADDQ IA QSLCGED LIIKGISVHI SNAEPKHNSN RQLERSGRFG GNPGGFGNQG GFGNSRGGGA GLGNNQGSNM GGGMNFGAFS INP AMMAAA QAALQSSWGM MGMLASQQNQ SGPSGNNQNQ GNMQREPNQA FGSGNNSYSG SNSGAAIGWG SASNAGSGSG FNGG FGSSM DSKSSGWGM

UniProtKB: TAR DNA-binding protein 43

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statehelical array

-
Sample preparation

BufferpH: 7.4
GridModel: C-flat-1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 85 % / Instrument: GATAN CRYOPLUNGE 3

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Number real images: 1641 / Average exposure time: 10.0 sec. / Average electron dose: 52.08 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 4.792 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.802 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 4.05 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1.1) / Number images used: 26881
Segment selectionNumber selected: 26881 / Software - Name: RELION (ver. 3.1.1)
Startup modelType of model: NONE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

-
Atomic model buiding 1

RefinementSpace: REAL / Protocol: BACKBONE TRACE / Target criteria: correlation coefficient
Output model

PDB-8qxa:
TDP-43 amyloid fibrils: Morphology-1b

+
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