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Yorodumi- PDB-6cew: Segment AMMAAA from the low complexity domain of TDP-43, residues... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6cew | ||||||
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Title | Segment AMMAAA from the low complexity domain of TDP-43, residues 321-326 | ||||||
Components | AMMAAA | ||||||
Keywords | PROTEIN FIBRIL / Amyloid / Steric-zipper | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.2 Å | ||||||
Authors | Guenther, E.L. / Cao, Q. / Lu, J. / Sawaya, M.R. / Eisenberg, D.S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2018 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6cew.cif.gz | 13.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cew.ent.gz | 6.9 KB | Display | PDB format |
PDBx/mmJSON format | 6cew.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cew_validation.pdf.gz | 411.4 KB | Display | wwPDB validaton report |
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Full document | 6cew_full_validation.pdf.gz | 411.3 KB | Display | |
Data in XML | 6cew_validation.xml.gz | 2.6 KB | Display | |
Data in CIF | 6cew_validation.cif.gz | 2.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ce/6cew ftp://data.pdbj.org/pub/pdb/validation_reports/ce/6cew | HTTPS FTP |
-Related structure data
Related structure data | 7466C 7467C 8857C 5whnC 5whpC 5wiaC 5wiqC 5wkbC 5wkdC 6cb9C 6cf4C 6cfhC C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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-Components
#1: Protein/peptide | Mass: 564.718 Da / Num. of mol.: 2 / Fragment: residues 321-326 / Source method: obtained synthetically Details: Synthetic peptide AMMAAA corresponding to segment 321-326 of TDP-43 Source: (synth.) Homo sapiens (human) #2: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.43 Å3/Da |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.3 Details: 1.3 M ammonium phosphate, 0.1 M sodium acetate pH 6.3 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9791 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 1, 2017 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9791 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.2→22.05 Å / Num. obs: 2209 / % possible obs: 96 % / Redundancy: 3.507 % / Biso Wilson estimate: 12.836 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.181 / Rrim(I) all: 0.214 / Χ2: 0.781 / Net I/σ(I): 3.16 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: IDEAL BETA STRAND Resolution: 1.2→22.05 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.955 / SU B: 2.286 / SU ML: 0.045 / SU R Cruickshank DPI: 0.0612 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.061 / ESU R Free: 0.054 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 25.38 Å2 / Biso mean: 9.425 Å2 / Biso min: 6.16 Å2
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Refinement step | Cycle: final / Resolution: 1.2→22.05 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.201→1.232 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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