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- PDB-5wkd: Crystal structure of the segment, GNNQGSN, from the low complexit... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5wkd | ||||||
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Title | Crystal structure of the segment, GNNQGSN, from the low complexity domain of TDP-43, residues 300-306 | ||||||
![]() | TAR DNA-binding protein 43 | ||||||
![]() | PROTEIN FIBRIL / TDP-43 / amyloid / low complexity domain | ||||||
Function / homology | ![]() nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded 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 non-membrane-bounded organelle / negative regulation by host of viral transcription / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing / negative regulation of protein phosphorylation / molecular condensate scaffold activity / mRNA 3'-UTR binding / regulation of protein stability / regulation of circadian rhythm / positive regulation of insulin secretion / mRNA processing / cytoplasmic stress granule / positive regulation of protein import into nucleus / 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 / mitochondrion / DNA binding / RNA binding / nucleoplasm / identical protein binding / nucleus Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Guenther, E.L. / Trinh, H. / Sawaya, M.R. / Cascio, D. / Eisenberg, D.S. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation. Authors: Elizabeth L Guenther / Qin Cao / Hamilton Trinh / Jiahui Lu / Michael R Sawaya / Duilio Cascio / David R Boyer / Jose A Rodriguez / Michael P Hughes / David S Eisenberg / ![]() Abstract: The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is ...The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 9.1 KB | Display | ![]() |
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PDB format | ![]() | 4.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 371.3 KB | Display | ![]() |
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Full document | ![]() | 371.3 KB | Display | |
Data in XML | ![]() | 2.3 KB | Display | |
Data in CIF | ![]() | 2.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7466C ![]() 7467C ![]() 8857C ![]() 5whnC ![]() 5whpC ![]() 5wiaC ![]() 5wiqC ![]() 5wkbC ![]() 6cb9C ![]() 6cewC ![]() 6cf4C ![]() 6cfhC C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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Unit cell |
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Components on special symmetry positions |
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Components
#1: Protein/peptide | Mass: 689.634 Da / Num. of mol.: 1 / Fragment: UNP residues 300-306 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#2: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 1.26 Å3/Da / Density % sol: 2.45 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 100mM Bis-Tris propane, pH 7.5, 200 mM sodium sulfate, 20% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 13, 2014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9791 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.8→100 Å / Num. obs: 373 / % possible obs: 91.6 % / Redundancy: 2.3 % / Rmerge(I) obs: 0.158 / Χ2: 2.003 / Net I/σ(I): 5.4 / Num. measured all: 845 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: idealized beta strand Resolution: 1.8→24.65 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.95 / WRfactor Rfree: 0.1803 / WRfactor Rwork: 0.1674 / FOM work R set: 0.8177 / SU B: 3.915 / SU ML: 0.114 / SU R Cruickshank DPI: 0.2052 / SU Rfree: 0.1412 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.205 / ESU R Free: 0.141 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 24.53 Å2 / Biso mean: 8.826 Å2 / Biso min: 4.44 Å2
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Refinement step | Cycle: final / Resolution: 1.8→24.65 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.802→1.849 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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