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Yorodumi- PDB-8cyy: CryoEM structure of amplified alpha-synuclein fibril class B mixe... -
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-Basic information
Entry | Database: PDB / ID: 8cyy | ||||||
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Title | CryoEM structure of amplified alpha-synuclein fibril class B mixed type I/II with extended core from DLB case V | ||||||
Components | Alpha-synuclein | ||||||
Keywords | PROTEIN FIBRIL / alpha-synuclein / Cerebrospinal Fluid (CSF) / DLB | ||||||
Function / homology | Function and homology information regulation of phospholipase activity / negative regulation of monooxygenase activity / negative regulation of mitochondrial electron transport, NADH to ubiquinone / positive regulation of glutathione peroxidase activity / 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 ...regulation of phospholipase activity / negative regulation of monooxygenase activity / negative regulation of mitochondrial electron transport, NADH to ubiquinone / positive regulation of glutathione peroxidase activity / 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 transporter activity / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / regulation of reactive oxygen species biosynthetic process / regulation of synaptic vesicle recycling / 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 / response to iron(II) ion / regulation of norepinephrine uptake / 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 / synaptic vesicle transport / dynein complex binding / dopamine uptake involved in synaptic transmission / positive regulation of receptor recycling / regulation of dopamine secretion / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / cuprous ion binding / response to type II interferon / synaptic vesicle exocytosis / positive regulation of exocytosis / kinesin binding / positive regulation of endocytosis / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / mitochondrial ATP synthesis coupled electron transport / response to magnesium ion / synaptic vesicle endocytosis / regulation of presynapse assembly / negative regulation of serotonin uptake / alpha-tubulin binding / phospholipid metabolic process / supramolecular fiber organization / axon terminus / inclusion body / cellular response to copper ion / cellular response to epinephrine stimulus / Hsp70 protein binding / response to interleukin-1 / : / adult locomotory behavior / positive regulation of release of sequestered calcium ion into cytosol / SNARE binding / excitatory postsynaptic potential / fatty acid metabolic process / long-term synaptic potentiation / phosphoprotein binding / protein tetramerization / regulation of transmembrane transporter activity / negative regulation of protein kinase activity / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / protein destabilization / ferrous iron binding / tau protein binding / positive regulation of protein serine/threonine kinase activity / PKR-mediated signaling / receptor internalization / phospholipid binding / : / synaptic vesicle membrane / positive regulation of inflammatory response / actin cytoskeleton / positive regulation of peptidyl-serine phosphorylation / actin binding / cellular response to oxidative stress / histone binding / cell cortex / growth cone / chemical synaptic transmission / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynapse / amyloid fibril formation / response to lipopolysaccharide / molecular adaptor activity / lysosome / oxidoreductase activity / transcription cis-regulatory region binding / positive regulation of apoptotic process Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Zhou, Y. / Sokratian, A. / Xu, E. / Viverette, E. / Dillard, L. / Yuan, Y. / Li, J.Y. / Matarangas, A. / Bouvette, J. / Borgnia, M. ...Zhou, Y. / Sokratian, A. / Xu, E. / Viverette, E. / Dillard, L. / Yuan, Y. / Li, J.Y. / Matarangas, A. / Bouvette, J. / Borgnia, M. / Bartesaghi, A. / West, A. | ||||||
Funding support | United States, 1items
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Citation | Journal: To Be Published Title: Structural and functional landscape of alpha-synuclein fibril assemblies amplified from cerebrospinal fluid Authors: Zhou, Y. / Sokratian, A. / Xu, E. / Viverette, E. / Dillard, L. / Yuan, Y. / Li, J.Y. / Matarangas, A. / Bouvette, J. / Borgnia, M. / Bartesaghi, A. / West, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8cyy.cif.gz | 171.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8cyy.ent.gz | 112.7 KB | Display | PDB format |
PDBx/mmJSON format | 8cyy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8cyy_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8cyy_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8cyy_validation.xml.gz | 31.7 KB | Display | |
Data in CIF | 8cyy_validation.cif.gz | 49 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cy/8cyy ftp://data.pdbj.org/pub/pdb/validation_reports/cy/8cyy | HTTPS FTP |
-Related structure data
Related structure data | 27088MC 8cysC 8cytC 8cyvC 8cywC 8cyxC 8cz0C 8cz1C 8cz2C 8cz3C 8cz6C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
NCS oper:
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-Components
#1: Protein | Mass: 14476.108 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SNCA, NACP, PARK1 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: P37840 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Amplified alpha-synuclein fibrils from Lewy body dementia CSF Type: ORGANELLE OR CELLULAR COMPONENT Details: alpha-synuclein fibril produced in presence of postmortem cerebrospinal fluid from specimens affected by synucleinopathies Entity ID: all / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Value: 60 kDa/nm / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) / Tissue: cerebrospinal fluid | |||||||||||||||||||||||||
Source (recombinant) | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) Plasmid: pRK172 | |||||||||||||||||||||||||
Buffer solution | pH: 7.4 / Details: Gibco Cat # 10010072 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 90 % |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -0.71 ° / Axial rise/subunit: 4.8 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 164382 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 31.05 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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Refine LS restraints NCS |
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