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- PDB-6n3b: SegA-asym, conformation of TDP-43 low complexity domain segment A asym -
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Open data
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Basic information
Entry | Database: PDB / ID: 6n3b | ||||||
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Title | SegA-asym, conformation of TDP-43 low complexity domain segment A asym | ||||||
![]() | TAR DNA-binding protein 43 | ||||||
![]() | dna binding protein / protein fibril / Amyloid / TDP43 / ALS / FTLD-TDP | ||||||
Function / homology | ![]() nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / negative regulation by host of viral transcription / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded organelle / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing ...nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / negative regulation by host of viral transcription / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded organelle / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing / molecular condensate scaffold activity / negative regulation of protein phosphorylation / mRNA 3'-UTR binding / 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 | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.8 Å | ||||||
![]() | Cao, Q. / Boyer, D.R. / Sawaya, M.R. / Eisenberg, D.S. | ||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 68.2 KB | Display | ![]() |
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PDB format | ![]() | 52.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9350MC ![]() 0334C ![]() 9339C ![]() 9349C ![]() 6n37C ![]() 6n3aC ![]() 6n3cC C: citing same article ( M: map data used to model this data |
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Similar structure data | |
EM raw data | ![]() 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]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein/peptide | Mass: 5207.797 Da / Num. of mol.: 10 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: TDP43 fibril / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2 nm / Nominal defocus min: 2 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Image recording | Average exposure time: 8 sec. / Electron dose: 48 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -2.27 ° / Axial rise/subunit: 4.81 Å / Axial symmetry: C1 | |||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 15464 / Symmetry type: HELICAL | |||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL |