+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-6988 | |||||||||
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Title | cryo-em structure of alpha-synuclein fiber | |||||||||
Map data | Density map calculated by applying a helical symmetry to the segments in the middle of 3D reconstruction. The twist angle is 179.64 degree and the rise is 3.39 angstrom. | |||||||||
Sample |
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Keywords | alpha-syn fiber / Parkinson disease / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process ...negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / negative regulation of transporter activity / negative regulation of chaperone-mediated autophagy / mitochondrial membrane organization / regulation of reactive oxygen species biosynthetic process / positive regulation of protein localization to cell periphery / regulation of synaptic vesicle recycling / negative regulation of platelet-derived growth factor receptor signaling pathway / negative regulation of exocytosis / regulation of glutamate secretion / response to iron(II) ion / regulation of norepinephrine uptake / dopamine biosynthetic process / SNARE complex assembly / positive regulation of neurotransmitter secretion / synaptic vesicle priming / dopamine uptake involved in synaptic transmission / regulation of macrophage activation / regulation of locomotion / mitochondrial ATP synthesis coupled electron transport / positive regulation of inositol phosphate biosynthetic process / negative regulation of microtubule polymerization / synaptic vesicle transport / dynein complex binding / positive regulation of receptor recycling / regulation of dopamine secretion / positive regulation of endocytosis / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / response to type II interferon / cuprous ion binding / positive regulation of exocytosis / synaptic vesicle exocytosis / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / response to magnesium ion / kinesin binding / alpha-tubulin binding / regulation of presynapse assembly / synaptic vesicle endocytosis / negative regulation of serotonin uptake / localization / phospholipid metabolic process / supramolecular fiber organization / axon terminus / inclusion body / cellular response to copper ion / Hsp70 protein binding / cellular response to epinephrine stimulus / excitatory postsynaptic potential / response to interleukin-1 / adult locomotory behavior / SNARE binding / positive regulation of release of sequestered calcium ion into cytosol / fatty acid metabolic process / long-term synaptic potentiation / regulation of transmembrane transporter activity / ferrous iron binding / synapse organization / phospholipid binding / protein tetramerization / phosphoprotein binding / microglial cell activation / regulation of long-term neuronal synaptic plasticity / negative regulation of protein kinase activity / tau protein binding / protein destabilization / PKR-mediated signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of protein serine/threonine kinase activity / receptor internalization / synaptic vesicle membrane / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / actin cytoskeleton / positive regulation of peptidyl-serine phosphorylation / cellular response to oxidative stress / actin binding / cell cortex / growth cone / histone binding / chemical synaptic transmission / postsynapse / neuron apoptotic process / negative regulation of neuron apoptotic process / amyloid fibril formation / response to lipopolysaccharide / lysosome / oxidoreductase activity / molecular adaptor activity / transcription cis-regulatory region binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.07 Å | |||||||||
Authors | Li YW / Zhao CY | |||||||||
Citation | Journal: Cell Res / Year: 2018 Title: Amyloid fibril structure of α-synuclein determined by cryo-electron microscopy. Authors: Yaowang Li / Chunyu Zhao / Feng Luo / Zhenying Liu / Xinrui Gui / Zhipu Luo / Xiang Zhang / Dan Li / Cong Liu / Xueming Li / Abstract: α-Synuclein (α-syn) amyloid fibrils are the major component of Lewy bodies, which are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. High-resolution structure of ...α-Synuclein (α-syn) amyloid fibrils are the major component of Lewy bodies, which are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. High-resolution structure of α-syn fibril is important for understanding its assembly and pathological mechanism. Here, we determined a fibril structure of full-length α-syn (1-140) at the resolution of 3.07 Å by cryo-electron microscopy (cryo-EM). The fibrils are cytotoxic, and transmissible to induce endogenous α-syn aggregation in primary neurons. Based on the reconstructed cryo-EM density map, we were able to unambiguously build the fibril structure comprising residues 37-99. The α-syn amyloid fibril structure shows two protofilaments intertwining along an approximate 2 screw axis into a left-handed helix. Each protofilament features a Greek key-like topology. Remarkably, five out of the six early-onset PD familial mutations are located at the dimer interface of the fibril (H50Q, G51D, and A53T/E) or involved in the stabilization of the protofilament (E46K). Furthermore, these PD mutations lead to the formation of fibrils with polymorphic structures distinct from that of the wild-type. Our study provides molecular insight into the fibrillar assembly of α-syn at the atomic level and sheds light on the molecular pathogenesis caused by familial PD mutations of α-syn. | |||||||||
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_6988.map.gz | 8.4 MB | EMDB map data format | |
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Header (meta data) | emd-6988-v30.xml emd-6988.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
Images | emd_6988.png | 139.6 KB | ||
Filedesc metadata | emd-6988.cif.gz | 5.2 KB | ||
Others | emd_6988_additional.map.gz emd_6988_half_map_1.map.gz emd_6988_half_map_2.map.gz | 28.4 MB 23.4 MB 23.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-6988 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6988 | HTTPS FTP |
-Related structure data
Related structure data | 6a6bMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_6988.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Density map calculated by applying a helical symmetry to the segments in the middle of 3D reconstruction. The twist angle is 179.64 degree and the rise is 3.39 angstrom. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.32 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: 3D reconstruction map without applying helical symmetry.
File | emd_6988_additional.map | ||||||||||||
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Annotation | 3D reconstruction map without applying helical symmetry. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 3D reconstruction map using half dataset
File | emd_6988_half_map_1.map | ||||||||||||
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Annotation | 3D reconstruction map using half dataset | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: 3D reconstruction map using half dataset
File | emd_6988_half_map_2.map | ||||||||||||
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Annotation | 3D reconstruction map using half dataset | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : alpha-synuclein fiber
Entire | Name: alpha-synuclein fiber |
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Components |
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-Supramolecule #1: alpha-synuclein fiber
Supramolecule | Name: alpha-synuclein fiber / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Alpha-synuclein
Macromolecule | Name: Alpha-synuclein / type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 6.251097 KDa |
Recombinant expression | Organism: Escherichia coli K-12 (bacteria) |
Sequence | String: VLYVGSKTKE GVVHGVATVA EKTKEQVTNV GGAVVTGVTA VAQKTVEGAG SIAAATGFVK KDQ UniProtKB: Alpha-synuclein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE Details: 4 microl of alpha-syn fibril solution was applied to a glow-discharged holey carbon grid (Quantifoil R1.2/1.3, 300 mesh), blotted for 6 s, and plunge-frozen in liquid ethane using FEI ...Details: 4 microl of alpha-syn fibril solution was applied to a glow-discharged holey carbon grid (Quantifoil R1.2/1.3, 300 mesh), blotted for 6 s, and plunge-frozen in liquid ethane using FEI Vitrobot Mark IV. 95% humidity, 16 degrees |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 289 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-32 / Average exposure time: 8.0 sec. / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: a feature less cylinder |
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Final angle assignment | Type: NOT APPLICABLE |
Final reconstruction | Applied symmetry - Helical parameters - Δz: 2.393 Å Applied symmetry - Helical parameters - Δ&Phi: 179.641 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Resolution.type: BY AUTHOR / Resolution: 3.07 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2.1) / Number images used: 43677 |