+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0334 | |||||||||
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Title | SegB, conformation of TDP-43 low complexity domain segment A | |||||||||
Map data | None | |||||||||
Sample |
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Keywords | Amyloid / TDP43 / ALS / FTLD-TDP / dna binding protein / 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 protein stability / positive regulation of insulin secretion / regulation of circadian rhythm / positive regulation of protein import into nucleus / mRNA processing / cytoplasmic stress granule / rhythmic process / regulation of gene expression / double-stranded DNA binding / 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 | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Cao Q / Boyer DR | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2019 Title: Cryo-EM structures of four polymorphic TDP-43 amyloid cores. Authors: Qin Cao / David R Boyer / Michael R Sawaya / Peng Ge / David S Eisenberg / Abstract: The DNA and RNA processing protein TDP-43 undergoes both functional and pathogenic aggregation. Functional TDP-43 aggregates form reversible, transient species such as nuclear bodies, stress ...The DNA and RNA processing protein TDP-43 undergoes both functional and pathogenic aggregation. Functional TDP-43 aggregates form reversible, transient species such as nuclear bodies, stress granules, and myo-granules. Pathogenic, irreversible TDP-43 aggregates form in amyotrophic lateral sclerosis and other neurodegenerative conditions. Here we find the features of TDP-43 fibrils that confer both reversibility and irreversibility by determining structures of two segments reported to be the pathogenic cores of human TDP-43 aggregation: SegA (residues 311-360), which forms three polymorphs, all with dagger-shaped folds; and SegB A315E (residues 286-331 containing the amyotrophic lateral sclerosis hereditary mutation A315E), which forms R-shaped folds. Energetic analysis suggests that the dagger-shaped polymorphs represent irreversible fibril structures, whereas the SegB polymorph may participate in both reversible and irreversible fibrils. Our structures reveal the polymorphic nature of TDP-43 and suggest how the A315E mutation converts the R-shaped polymorph to an irreversible form that enhances pathology. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0334.map.gz | 7.3 MB | EMDB map data format | |
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Header (meta data) | emd-0334-v30.xml emd-0334.xml | 10.5 KB 10.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0334_fsc.xml | 11.3 KB | Display | FSC data file |
Images | emd_0334.png | 28 KB | ||
Filedesc metadata | emd-0334.cif.gz | 5.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0334 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0334 | HTTPS FTP |
-Validation report
Summary document | emd_0334_validation.pdf.gz | 598.6 KB | Display | EMDB validaton report |
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Full document | emd_0334_full_validation.pdf.gz | 598.2 KB | Display | |
Data in XML | emd_0334_validation.xml.gz | 11.2 KB | Display | |
Data in CIF | emd_0334_validation.cif.gz | 15 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0334 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0334 | HTTPS FTP |
-Related structure data
Related structure data | 6n3cMC 9339C 9349C 9350C 6n37C 6n3aC 6n3bC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | |
EM raw data | EMPIAR-10497 (Title: Cryo-EM structures of four polymorphic TDP-43 amyloid cores Data size: 4.5 TB Data #1: Unaligned dose fractionated frames of TDP-43 SegA amyloid fibrils [micrographs - multiframe] Data #2: Unaligned dose fractionated frames of TDP-43 SegB A315E amyloid fibrils [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0334.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : TDP43 fibril
Entire | Name: TDP43 fibril |
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Components |
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-Supramolecule #1: TDP43 fibril
Supramolecule | Name: TDP43 fibril / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: TAR DNA-binding protein 43
Macromolecule | Name: TAR DNA-binding protein 43 / type: protein_or_peptide / ID: 1 / Number of copies: 20 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 4.404797 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: QGGFGNSRGG GAGLGNNQGS NMGGGMNFGE FSINPAMMAA AQAALQ UniProtKB: TAR DNA-binding protein 43 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average exposure time: 8.0 sec. / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 0.002 µm / Nominal defocus min: 0.002 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | PDB-6n3c: |