[English] 日本語
Yorodumi- EMDB-8857: MicroED structure of the segment, NFGEFS, from the A315E familial... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-8857 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | MicroED structure of the segment, NFGEFS, from the A315E familial variant of the low complexity domain of TDP-43, residues 312-317 | |||||||||
Map data | NFGEFS from the A315E familial variant of the low complexity domain of TDP-43, residues 312-317 | |||||||||
Sample |
| |||||||||
Keywords | Amyloid / LARKS / TDP-43 / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information 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 / mRNA 3'-UTR binding / molecular condensate scaffold activity / 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 | Homo sapiens (human) | |||||||||
Method | electron crystallography / cryo EM / Resolution: 1.0 Å | |||||||||
Authors | Guenther EL / Sawaya MR | |||||||||
Funding support | United States, 1 items
| |||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_8857.map.gz | 107.3 KB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-8857-v30.xml emd-8857.xml | 11.2 KB 11.2 KB | Display Display | EMDB header |
Images | emd_8857.png | 350.5 KB | ||
Filedesc metadata | emd-8857.cif.gz | 4.6 KB | ||
Filedesc structureFactors | emd_8857_sf.cif.gz | 31.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8857 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8857 | HTTPS FTP |
-Validation report
Summary document | emd_8857_validation.pdf.gz | 320.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_8857_full_validation.pdf.gz | 319.7 KB | Display | |
Data in XML | emd_8857_validation.xml.gz | 3.9 KB | Display | |
Data in CIF | emd_8857_validation.cif.gz | 4.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8857 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8857 | HTTPS FTP |
-Related structure data
Related structure data | 5wkbMC 7466C 7467C 5whnC 5whpC 5wiaC 5wiqC 5wkdC 6cb9C 6cewC 6cf4C 6cfhC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_8857.map.gz / Format: CCP4 / Size: 116.2 KB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | NFGEFS from the A315E familial variant of the low complexity domain of TDP-43, residues 312-317 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X: 0.32402 Å / Y: 0.335 Å / Z: 0.30625 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 18 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : Segment from TDP-43
Entire | Name: Segment from TDP-43 |
---|---|
Components |
|
-Supramolecule #1: Segment from TDP-43
Supramolecule | Name: Segment from TDP-43 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: TAR DNA-binding protein 43
Macromolecule | Name: TAR DNA-binding protein 43 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 699.709 Da |
Sequence | String: NFGEFS UniProtKB: TAR DNA-binding protein 43 |
-Macromolecule #2: water
Macromolecule | Name: water / type: ligand / ID: 2 / Number of copies: 2 / Formula: HOH |
---|---|
Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | electron crystallography |
Aggregation state | 3D array |
-Sample preparation
Buffer | pH: 7.5 / Component - Name: 1x PBS / Details: 1x PBS, pH 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI F20 |
---|---|
Image recording | Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Digitization - Dimensions - Width: 2048 pixel / Digitization - Dimensions - Height: 2048 pixel / Average electron dose: 3.4 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Camera length: 1840 mm |
Sample stage | Specimen holder model: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Tecnai F20 / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 1.0 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES |
---|---|
Molecular replacement | Software - Name: SHELXD |
Merging software list | Software - Name: XSCALE |
Crystallography statistics | Number intensities measured: 18942 / Number structure factors: 2032 / Fourier space coverage: 88.7 / R sym: 28.3 / R merge: 28.3 / Overall phase error: 0.001 / Overall phase residual: 0.001 / Phase error rejection criteria: 1 / High resolution: 1.0 Å / Shell - Shell ID: 1 / Shell - High resolution: 1.0 Å / Shell - Low resolution: 1.03 Å / Shell - Number structure factors: 110 / Shell - Phase residual: 0.001 / Shell - Fourier space coverage: 78 / Shell - Multiplicity: 4.8 |