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- EMDB-7619: Alpha Synuclein fibril formed by full length protein - Twister Po... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7619 | ||||||||||||
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Title | Alpha Synuclein fibril formed by full length protein - Twister Polymorph | ||||||||||||
![]() | primary map | ||||||||||||
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Function / homology | ![]() negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | helical reconstruction / ![]() | ||||||||||||
![]() | Li B / Hatami A | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel. Authors: Binsen Li / Peng Ge / Kevin A Murray / Phorum Sheth / Meng Zhang / Gayatri Nair / Michael R Sawaya / Woo Shik Shin / David R Boyer / Shulin Ye / David S Eisenberg / Z Hong Zhou / Lin Jiang / ![]() Abstract: α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn ...α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 25.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.9 KB 14.9 KB | Display Display | ![]() |
Images | ![]() | 191.1 KB | ||
Masks | ![]() | 27 MB | ![]() | |
Filedesc metadata | ![]() | 6.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6cu8MC ![]() 7618C ![]() 6cu7C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Alpha-synuclein fibril - twister polymorph
Entire | Name: Alpha-synuclein fibril - twister polymorph |
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Components |
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-Supramolecule #1: Alpha-synuclein fibril - twister polymorph
Supramolecule | Name: Alpha-synuclein fibril - twister polymorph / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Alpha-synuclein
Macromolecule | Name: Alpha-synuclein / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 14.476108 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIA AATGFVKKDQ LGKNEEGAPQ EGILEDMPVD PDNEAYEMPS EEGYQDYEPE A UniProtKB: ![]() |
-Experimental details
-Structure determination
Method | ![]() |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 3 / Component - Concentration: 15.0 mM / Component - Formula: C16H36BrP / Component - Name: tetrabutylphosphonium bromide |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 240 sec. / Pretreatment - Atmosphere: AIR Details: Quantifoil grid was treated with 1,2-Dichloroethane for one week, coated with additional carbon, and baken under 120kV in Camera chamber for 3 days |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV / Details: blot force: 1 blot time: 4s. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus max: 4.0 µm / Calibrated defocus min: 1.5 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Lower energy threshold: -10 eV / Energy filter - Upper energy threshold: 10 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Temperature | Min: 77.0 K / Max: 77.0 K |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 3-20 / Number grids imaged: 1 / Number real images: 1821 / Average exposure time: 10.0 sec. / Average electron dose: 30.0 e/Å2 / Details: Frame rate 5 Hz |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Segment selection | Number selected: 182253 / Software - Name: EMAN (ver. 1.8) |
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Startup model | Type of model: NONE Details: A elongated Gaussian blob was used for initial model. |
Final angle assignment | Type: NOT APPLICABLE / Software - Name: RELION (ver. 2.0) |
Final reconstruction | Applied symmetry - Helical parameters - Δz: 2.4 Å Applied symmetry - Helical parameters - Δ&Phi: 179.06 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 2.0) / Number images used: 34091 |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-6cu8: |