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- PDB-5wia: Crystal structure of the segment, GNNSYS, from the low complexity... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5wia | ||||||
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Title | Crystal structure of the segment, GNNSYS, from the low complexity domain of TDP-43, residues 370-375 | ||||||
![]() | TAR DNA-binding protein 43 | ||||||
![]() | PROTEIN FIBRIL / Amyloid / TDP-43 | ||||||
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 / positive regulation of protein import into nucleus / 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 / mitochondrion / DNA binding / RNA binding / nucleoplasm / identical protein binding / nucleus Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Guenther, E.L. / Trinh, H. / Sawaya, M.R. / 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 | ![]() | 10.7 KB | Display | ![]() |
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PDB format | ![]() | 5.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 371.8 KB | Display | ![]() |
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Full document | ![]() | 371.8 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 ![]() 5wiqC ![]() 5wkbC ![]() 5wkdC ![]() 6cb9C ![]() 6cewC ![]() 6cf4C ![]() 6cfhC C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein/peptide | Mass: 640.602 Da / Num. of mol.: 1 / Fragment: UNP residues 370-375 / Source method: obtained synthetically Details: Synthetic peptide GNNSYS corresponding to segment 370-375 of TDP-43 Source: (synth.) ![]() |
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#2: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 100mM bis tris propane 8.5, 200mM sodium nitrate, 20% PEG 3350 |
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-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 18, 2015 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9791 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1→100 Å / Num. obs: 1864 / % possible obs: 95.2 % / Redundancy: 5.4 % / Biso Wilson estimate: 2.69 Å2 / Rmerge(I) obs: 0.155 / Rpim(I) all: 0.072 / Rrim(I) all: 0.172 / Χ2: 1.191 / Net I/σ(I): 5.2 / Num. measured all: 10032 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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Processing
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Refinement | Method to determine structure: ![]() Starting model: ideal 5-residue polyalanine beta-strand Resolution: 1.002→20.34 Å / SU ML: 0.07 / Cross valid method: FREE R-VALUE / σ(F): 1.39 / Phase error: 17.13
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||
Displacement parameters | Biso max: 15.34 Å2 / Biso mean: 3.7159 Å2 / Biso min: 1.17 Å2 | ||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.002→20.34 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.0016→20.3437 Å / Rfactor Rfree error: 0 / Total num. of bins used: 1
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