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Open data
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Basic information
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Title | Lipidic alpha-synuclein fibril - polymorph L1B | |||||||||||||||
![]() | Lipidic alpha-synuclein fibril - polymorph L1B | |||||||||||||||
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![]() | amyloid fibril / PROTEIN FIBRIL | |||||||||||||||
Function / homology | ![]() negative regulation of mitochondrial electron transport, NADH to ubiquinone / : / response to desipramine / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber ...negative regulation of mitochondrial electron transport, NADH to ubiquinone / : / response to desipramine / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / mitochondrial membrane organization / regulation of synaptic vesicle recycling / negative regulation of chaperone-mediated autophagy / regulation of reactive oxygen species biosynthetic process / negative regulation of platelet-derived growth factor receptor signaling pathway / positive regulation of protein localization to cell periphery / negative regulation of exocytosis / regulation of glutamate secretion / SNARE complex assembly / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / response to iron(II) ion / regulation of norepinephrine uptake / negative regulation of dopamine metabolic process / regulation of locomotion / mitochondrial ATP synthesis coupled electron transport / regulation of macrophage activation / positive regulation of inositol phosphate biosynthetic process / synaptic vesicle priming / transporter regulator activity / negative regulation of microtubule polymerization / synaptic vesicle transport / positive regulation of receptor recycling / dopamine uptake involved in synaptic transmission / protein kinase inhibitor activity / dynein complex binding / regulation of dopamine secretion / negative regulation of thrombin-activated receptor signaling pathway / nuclear outer membrane / cuprous ion binding / positive regulation of exocytosis / synaptic vesicle exocytosis / response to magnesium ion / positive regulation of endocytosis / kinesin binding / synaptic vesicle endocytosis / enzyme inhibitor activity / cysteine-type endopeptidase inhibitor activity / negative regulation of serotonin uptake / regulation of presynapse assembly / response to type II interferon / alpha-tubulin binding / beta-tubulin binding / phospholipase binding / behavioral response to cocaine / supramolecular fiber organization / cellular response to copper ion / phospholipid metabolic process / cellular response to fibroblast growth factor stimulus / inclusion body / axon terminus / cellular response to epinephrine stimulus / Hsp70 protein binding / response to interleukin-1 / regulation of microtubule cytoskeleton organization / SNARE binding / positive regulation of release of sequestered calcium ion into cytosol / adult locomotory behavior / excitatory postsynaptic potential / phosphoprotein binding / protein tetramerization / fatty acid metabolic process / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / ferrous iron binding / protein destabilization / PKR-mediated signaling / phospholipid binding / receptor internalization / tau protein binding / long-term synaptic potentiation / terminal bouton / positive regulation of inflammatory response / synaptic vesicle membrane / actin cytoskeleton / actin binding / growth cone / cellular response to oxidative stress / cell cortex / neuron apoptotic process / microtubule binding / response to lipopolysaccharide / chemical synaptic transmission / molecular adaptor activity / amyloid fibril formation / histone binding / negative regulation of neuron apoptotic process / mitochondrial outer membrane / lysosome Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.98 Å | |||||||||||||||
![]() | Frieg B / Antonschmidt L / Dienemann C / Geraets JA / Najbauer EE / Matthes D / de Groot BL / Andreas LB / Becker S / Griesinger C / Schroeder GF | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: The 3D structure of lipidic fibrils of α-synuclein. Authors: Benedikt Frieg / Leif Antonschmidt / Christian Dienemann / James A Geraets / Eszter E Najbauer / Dirk Matthes / Bert L de Groot / Loren B Andreas / Stefan Becker / Christian Griesinger / Gunnar F Schröder / ![]() Abstract: α-synuclein misfolding and aggregation into fibrils is a common feature of α-synucleinopathies, such as Parkinson's disease, in which α-synuclein fibrils are a characteristic hallmark of neuronal ...α-synuclein misfolding and aggregation into fibrils is a common feature of α-synucleinopathies, such as Parkinson's disease, in which α-synuclein fibrils are a characteristic hallmark of neuronal inclusions called Lewy bodies. Studies on the composition of Lewy bodies extracted postmortem from brain tissue of Parkinson's patients revealed that lipids and membranous organelles are also a significant component. Interactions between α-synuclein and lipids have been previously identified as relevant for Parkinson's disease pathology, however molecular insights into their interactions have remained elusive. Here we present cryo-electron microscopy structures of six α-synuclein fibrils in complex with lipids, revealing specific lipid-fibril interactions. We observe that phospholipids promote an alternative protofilament fold, mediate an unusual arrangement of protofilaments, and fill the central cavities of the fibrils. Together with our previous studies, these structures also indicate a mechanism for fibril-induced lipid extraction, which is likely to be involved in the development of α-synucleinopathies. Specifically, one potential mechanism for the cellular toxicity is the disruption of intracellular vesicles mediated by fibrils and oligomers, and therefore the modulation of these interactions may provide a promising strategy for future therapeutic interventions. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 11.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.6 KB 14.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.9 KB | Display | ![]() |
Images | ![]() | 77.7 KB | ||
Filedesc metadata | ![]() | 5.2 KB | ||
Others | ![]() ![]() | 46 MB 46 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 898.5 KB | Display | ![]() |
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Full document | ![]() | 898 KB | Display | |
Data in XML | ![]() | 14.6 KB | Display | |
Data in CIF | ![]() | 20.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8advMC ![]() 8a4lC ![]() 8adsC ![]() 8aduC ![]() 8adwC ![]() 8aexC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | Lipidic alpha-synuclein fibril - polymorph L1B | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Lipidic alpha-synuclein fibril - polymorph L1B (half map 1)
File | emd_15371_half_map_1.map | ||||||||||||
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Annotation | Lipidic alpha-synuclein fibril - polymorph L1B (half map 1) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Lipidic alpha-synuclein fibril - polymorph L1B (half map 2)
File | emd_15371_half_map_2.map | ||||||||||||
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Annotation | Lipidic alpha-synuclein fibril - polymorph L1B (half map 2) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Lipidic alpha-synuclein fibril - polymorph L1B
Entire | Name: Lipidic alpha-synuclein fibril - polymorph L1B |
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Components |
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-Supramolecule #1: Lipidic alpha-synuclein fibril - polymorph L1B
Supramolecule | Name: Lipidic alpha-synuclein fibril - polymorph L1B / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-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: Alpha-synuclein |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.83 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |