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- PDB-5whn: Crystal structure of the segment, NFGAFS, from the low complexity... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5whn | ||||||
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Title | Crystal structure of the segment, NFGAFS, from the low complexity domain of TDP-43, residues 312-317 | ||||||
![]() | Segment of TAR DNA-binding protein 43 | ||||||
![]() | PROTEIN FIBRIL / ![]() ![]() ![]() | ||||||
Function / homology | ![]() nuclear inner membrane organization / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Guenther, E.L. / 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 11.3 KB | Display | ![]() |
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PDB format | ![]() | 5.8 KB | Display | ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7466C ![]() 7467C ![]() 8857C ![]() 5whpC ![]() 5wiaC ![]() 5wiqC ![]() 5wkbC ![]() 5wkdC ![]() 6cb9C ![]() 6cewC ![]() 6cf4C ![]() 6cfhC ![]() 3dgjS S: Starting model for refinement 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: 641.673 Da / Num. of mol.: 1 / Fragment: UNP residues 312-317 / Source method: obtained synthetically Details: Synthetic peptide NFGAFS corresponding tosegment 312-317 of TDP-43 Source: (synth.) ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal grow![]() | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 4.2 Details: 100mM phosphate/citrate 4.2, 40% ethanol, 5% PEG 1000 |
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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: Jun 20, 2014 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.1→13.253 Å / Num. obs: 1447 / % possible obs: 94 % / Observed criterion σ(I): -3 / Redundancy: 8.299 % / Biso Wilson estimate: 4.49 Å2 / CC1/2: 0.991 / Rmerge(I) obs: 0.172 / Rrim(I) all: 0.184 / Χ2: 0.955 / Net I/σ(I): 9.65 / Num. measured all: 12008 / Scaling rejects: 11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing![]() | Method: ![]() |
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Processing
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Refinement | Method to determine structure![]() ![]() Starting model: 3DGJ Resolution: 1.1→13.253 Å / SU ML: 0.07 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 14.3
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 8.39 Å2 / Biso mean: 4.55 Å2 / Biso min: 3.06 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.1→13.253 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.0995→13.2538 Å / Rfactor Rfree error: 0 / Total num. of bins used: 1
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Refinement TLS params. | Method: refined / Origin x: -2.6945 Å / Origin y: -1.2041 Å / Origin z: 6.5345 Å
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Refinement TLS group | Selection details: all |