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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-10307 | ||||||||||||||||||||||||||||||||||||||||||
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Title | cryo-em structure of alpha-synuclein fibril polymorph 2A | ||||||||||||||||||||||||||||||||||||||||||
![]() | Cryo-em of WT alpha-synuclein fibril polymorph 2A | ||||||||||||||||||||||||||||||||||||||||||
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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 / ![]() | ||||||||||||||||||||||||||||||||||||||||||
![]() | Guerrero-Ferreira R / Taylor NMI | ||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]() ![]() ![]()
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![]() | ![]() Title: Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy. Authors: Ricardo Guerrero-Ferreira / Nicholas Mi Taylor / Ana-Andreea Arteni / Pratibha Kumari / Daniel Mona / Philippe Ringler / Markus Britschgi / Matthias E Lauer / Ali Makky / Joeri Verasdonck / ...Authors: Ricardo Guerrero-Ferreira / Nicholas Mi Taylor / Ana-Andreea Arteni / Pratibha Kumari / Daniel Mona / Philippe Ringler / Markus Britschgi / Matthias E Lauer / Ali Makky / Joeri Verasdonck / Roland Riek / Ronald Melki / Beat H Meier / Anja Böckmann / Luc Bousset / Henning Stahlberg / ![]() ![]() ![]() Abstract: Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein ...Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, eLife 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability. | ||||||||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 6.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14 KB 14 KB | Display Display | ![]() |
Images | ![]() | 169.3 KB | ||
Filedesc metadata | ![]() | 5.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6ssxMC ![]() 4994C ![]() 4996C ![]() 6rt0C ![]() 6rtbC ![]() 6sstC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 90.9 Data #1: Aligned micrographs of alpha-synuclein fibrils [micrographs - single frame]) |
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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 | Cryo-em of WT alpha-synuclein fibril polymorph 2A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.629 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : alpha synuclein fibril, polymorph 2A
Entire | Name: alpha synuclein fibril, polymorph 2A |
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Components |
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-Supramolecule #1: alpha synuclein fibril, polymorph 2A
Supramolecule | Name: alpha synuclein fibril, polymorph 2A / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 51 kDa/nm |
-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
Concentration | 10 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK II Details: 3 uL aliquots were applied onto second glow-discharged 300 mesh copper Quantifoil grids R2 1. | |||||||||
Details | WT alpha synuclein |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 69.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER / Details: tube volume |
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Final angle assignment | Type: NOT APPLICABLE / Software - Name: RELION (ver. 2.1) |
Final reconstruction | Applied symmetry - Helical parameters - Δz: 4.8 Å Applied symmetry - Helical parameters - Δ&Phi: 0.8 ° Applied symmetry - Helical parameters - Axial symmetry: C2 (2 fold cyclic ![]() Resolution.type: BY AUTHOR / Resolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: ![]() |
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-6ssx: |