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Yorodumi- EMDB-31024: an arrested off-pathway oligomer of alpha-synuclein upon heme tre... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31024 | |||||||||
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Title | an arrested off-pathway oligomer of alpha-synuclein upon heme treatment after fibril formation | |||||||||
Map data | alpha-synuclein oligomer was formed upon heme treatment after alpha-synuclein fibril formation. | |||||||||
Sample |
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Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.9 Å | |||||||||
Authors | Dey S | |||||||||
Citation | Journal: Commun Biol / Year: 2021 Title: Conformational distortion in a fibril-forming oligomer arrests alpha-Synuclein fibrillation and minimizes its toxic effects. Authors: Ritobrita Chakraborty / Sandip Dey / Pallabi Sil / Simanta Sarani Paul / Dipita Bhattacharyya / Anirban Bhunia / Jayati Sengupta / Krishnananda Chattopadhyay / Abstract: The fibrillation pathway of alpha-Synuclein, the causative protein of Parkinson's disease, encompasses transient, heterogeneous oligomeric forms whose structural understanding and link to toxicity ...The fibrillation pathway of alpha-Synuclein, the causative protein of Parkinson's disease, encompasses transient, heterogeneous oligomeric forms whose structural understanding and link to toxicity are not yet understood. We report that the addition of the physiologically-available small molecule heme at a sub-stoichiometric ratio to either monomeric or aggregated α-Syn, targets a His50 residue critical for fibril-formation and stabilizes the structurally-heterogeneous populations of aggregates into a minimally-toxic oligomeric state. Cryo-EM 3D reconstruction revealed a 'mace'-shaped structure of this monodisperse population of oligomers, which is comparable to a solid-state NMR Greek key-like motif (where the core residues are arranged in parallel in-register sheets with a Greek key topology at the C terminus) that forms the fundamental unit/kernel of protofilaments. Further structural analyses suggest that heme binding induces a distortion in the Greek key-like architecture of the mace oligomers, which impairs their further appending into protofilaments and fibrils. Additionally, our study reports a novel mechanism of prevention as well as reclamation of amyloid fibril formation by blocking an inter-protofilament His50 residue using a small molecule. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_31024.map.gz | 1.3 MB | EMDB map data format | |
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Header (meta data) | emd-31024-v30.xml emd-31024.xml | 9.1 KB 9.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_31024_fsc.xml | 3.4 KB | Display | FSC data file |
Images | emd_31024.png | 69.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31024 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31024 | HTTPS FTP |
-Validation report
Summary document | emd_31024_validation.pdf.gz | 331.8 KB | Display | EMDB validaton report |
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Full document | emd_31024_full_validation.pdf.gz | 331.3 KB | Display | |
Data in XML | emd_31024_validation.xml.gz | 7.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31024 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31024 | HTTPS FTP |
-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_31024.map.gz / Format: CCP4 / Size: 1.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | alpha-synuclein oligomer was formed upon heme treatment after alpha-synuclein fibril formation. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.89 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : an arrested off-pathway oligomer of alpha-synuclein upon heme tre...
Entire | Name: an arrested off-pathway oligomer of alpha-synuclein upon heme treatment after fibril formation |
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Components |
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-Supramolecule #1: an arrested off-pathway oligomer of alpha-synuclein upon heme tre...
Supramolecule | Name: an arrested off-pathway oligomer of alpha-synuclein upon heme treatment after fibril formation type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Homo sapiens (human) / Organ: brain / Tissue: brain tissue / Location in cell: cytoplasm |
Recombinant expression | Organism: Escherichia coli DH1 (bacteria) / Recombinant strain: bl21 / Recombinant plasmid: pRK172 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 / Details: sodium phosphate buffer, pH 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI POLARA 300 |
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Image recording | Film or detector model: FEI EAGLE (4k x 4k) / Number grids imaged: 2 / Average exposure time: 2.0 sec. / Average electron dose: 20.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION |
Sample stage | Specimen holder model: GATAN 910 MULTI-SPECIMEN SINGLE TILT CRYO TRANSFER HOLDER Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |