- EMDB-6988: cryo-em structure of alpha-synuclein fiber -
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Open data
ID or keywords:
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Basic information
Entry
Database: EMDB / ID: EMD-6988
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
Complex: alpha-synuclein fiber
Protein or peptide: Alpha-synuclein
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 / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / 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 / regulation of norepinephrine uptake / response to iron(II) ion / SNARE complex assembly / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / regulation of locomotion / positive regulation of inositol phosphate biosynthetic process / synaptic vesicle priming / regulation of macrophage activation / negative regulation of microtubule polymerization / dopamine uptake involved in synaptic transmission / synaptic vesicle transport / dynein complex binding / positive regulation of receptor recycling / regulation of dopamine secretion / 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 / kinesin binding / positive regulation of endocytosis / mitochondrial ATP synthesis coupled electron transport / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / response to magnesium ion / regulation of presynapse assembly / synaptic vesicle endocytosis / negative regulation of serotonin uptake / alpha-tubulin binding / 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 / phosphoprotein binding / protein tetramerization / regulation of transmembrane transporter activity / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / negative regulation of protein kinase activity / protein destabilization / ferrous iron binding / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / PKR-mediated signaling / tau protein binding / positive regulation of protein serine/threonine kinase activity / receptor internalization / phospholipid binding / 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 / actin binding / cell cortex / histone binding / cellular response to oxidative stress / growth cone / postsynapse / chemical synaptic transmission / neuron apoptotic process / negative regulation of neuron apoptotic process / amyloid fibril formation / response to lipopolysaccharide / molecular adaptor activity / oxidoreductase activity / lysosome / transcription cis-regulatory region binding Similarity search - Function
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
Deposition
Jun 27, 2018
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Header (metadata) release
Jul 11, 2018
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Map release
Jul 11, 2018
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Update
Mar 27, 2024
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Current status
Mar 27, 2024
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Download / File: emd_6988.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
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
Contour Level
By AUTHOR: 0.02 / Movie #1: 0.02
Minimum - Maximum
-0.06977273 - 0.14746831
Average (Standard dev.)
0.001625986 (±0.008289028)
Symmetry
Space group: 1
Details
EMDB XML:
Map geometry
Axis order
X
Y
Z
Origin
0
0
0
Dimensions
200
200
200
Spacing
200
200
200
Cell
A=B=C: 264.0 Å α=β=γ: 90.0 °
CCP4 map header:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.32
1.32
1.32
M x/y/z
200
200
200
origin x/y/z
0.000
0.000
0.000
length x/y/z
264.000
264.000
264.000
α/β/γ
90.000
90.000
90.000
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
200
200
200
D min/max/mean
-0.070
0.147
0.002
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Supplemental data
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Additional map: 3D reconstruction map without applying helical symmetry.
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
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Electron microscopy
Microscope
FEI TITAN KRIOS
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
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
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