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- PDB-7xo3: Type 1C alpha-synuclein fibril seeded by cerebrospinal fluid from... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7xo3 | ||||||
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Title | Type 1C alpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-4) Parkinson's disease patient | ||||||
![]() | 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 | ![]() ![]() | ||||||
![]() | Fan, Y. / Sun, Y.P. / Wang, J. / Liu, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Conformational change of α-synuclein fibrils in cerebrospinal fluid from different clinical phases of Parkinson's disease. Authors: Yun Fan / Yunpeng Sun / Wenbo Yu / Youqi Tao / Wencheng Xia / Yiqi Liu / Qinyue Zhao / Yilin Tang / Yimin Sun / Fengtao Liu / Qin Cao / Jianjun Wu / Cong Liu / Jian Wang / Dan Li / ![]() Abstract: α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease ...α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease progression is unclear. Here, we amplified α-syn aggregates from the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) staged in preclinical PD (pre-PD), middle- to late-stage PD (mid-PD), and late-stage PD (late-PD). Our results show that α-syn fibrils derived from the late-PD patient are most potent in inducing endogenous α-syn aggregation in primary neurons, followed by the mid-PD and pre-PD fibrils. By using cryo-electron microscopy, we further determined the high-resolution structures of the CSF-amplified fibrils. The structures exhibit remarkable differences in a minor but significant population of conformational species in different staged samples. Our work demonstrates structural and pathological differences between α-syn fibrils derived from PD patients at a spectrum of clinical stages, which suggests potential conformational transition of α-syn fibrils during the progression of PD. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 68 KB | Display | ![]() |
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PDB format | ![]() | 51.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 33335MC ![]() 7v47C ![]() 7v48C ![]() 7v49C ![]() 7xo0C ![]() 7xo1C ![]() 7xo2C ![]() 8h03C ![]() 8h04C ![]() 8h05C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | ![]() Mass: 14476.108 Da / Num. of mol.: 6 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: Type 1C alpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-4) Parkinson's disease patient Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 6.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE |
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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![]() |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction![]() | Type: NONE |
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Helical symmerty | Angular rotation/subunit: 179.43 ° / Axial rise/subunit: 2.41 Å / Axial symmetry: C1 |
3D reconstruction![]() | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 120165 / Symmetry type: HELICAL |