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- PDB-6cu8: Alpha Synuclein fibril formed by full length protein - Twister Po... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6cu8 | ||||||||||||
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Title | Alpha Synuclein fibril formed by full length protein - Twister Polymorph | ||||||||||||
![]() | Alpha-synuclein![]() | ||||||||||||
![]() | PROTEIN FIBRIL / ![]() ![]() | ||||||||||||
Function / homology | ![]() negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ![]() ![]() | ||||||||||||
![]() | Li, B. / Hatami, A. / Ge, P. / Murray, K.A. / Sheth, P. / Zhang, M. / Nair, G. / Sawaya, M.R. / Zhu, C. / Broad, M. ...Li, B. / Hatami, A. / Ge, P. / Murray, K.A. / Sheth, P. / Zhang, M. / Nair, G. / Sawaya, M.R. / Zhu, C. / Broad, M. / Shin, W.S. / Ye, S. / John, V. / Eisenberg, D.S. / Zhou, Z.H. / Jiang, L. | ||||||||||||
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 | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 85.6 KB | Display | ![]() |
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PDB format | ![]() | 58.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7619MC ![]() 7618C ![]() 6cu7C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | ![]() Mass: 14476.108 Da / Num. of mol.: 10 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: Alpha-synuclein fibril - twister polymorph / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Units: MEGADALTONS / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 3 |
Buffer component | Conc.: 15 mM / Name: tetrabutylphosphonium bromide / Formula: C16H36BrP |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | 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 Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K / Details: blot force: 1 blot time: 4s |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 77 K / Temperature (min): 77 K |
Image recording | Average exposure time: 10 sec. / Electron dose: 30 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1821 / Details: Frame rate 5 Hz |
EM imaging optics | Energyfilter name![]() |
Image scans | Sampling size: 5 µm / Width: 3838 / Height: 3710 / Movie frames/image: 50 / Used frames/image: 3-20 |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 179.06 ° / Axial rise/subunit: 2.4 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 182253 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.6 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 34091 / Algorithm: BACK PROJECTION / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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