+Open data
-Basic information
Entry | Database: PDB / ID: 6shs | |||||||||
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Title | Abeta fibril (Morphology I) | |||||||||
Components | Amyloid-beta precursor protein | |||||||||
Keywords | PROTEIN FIBRIL / fibril / beta amyloid / Cryo-EM | |||||||||
Function / homology | Function and homology information regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity ...regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / positive regulation of amyloid fibril formation / neuron remodeling / : / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / suckling behavior / nuclear envelope lumen / dendrite development / COPII-coated ER to Golgi transport vesicle / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / regulation of presynapse assembly / transition metal ion binding / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / negative regulation of neuron differentiation / intracellular copper ion homeostasis / ECM proteoglycans / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / Mitochondrial protein degradation / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / cholesterol metabolic process / response to interleukin-1 / positive regulation of mitotic cell cycle / adult locomotory behavior / axonogenesis / extracellular matrix organization / positive regulation of peptidyl-threonine phosphorylation / platelet alpha granule lumen / trans-Golgi network membrane / dendritic shaft / learning / positive regulation of interleukin-1 beta production / locomotory behavior / positive regulation of long-term synaptic potentiation / central nervous system development / endosome lumen / astrocyte activation / positive regulation of JNK cascade / Post-translational protein phosphorylation / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / serine-type endopeptidase inhibitor activity / neuromuscular junction / recycling endosome / cognition / neuron cellular homeostasis / Golgi lumen / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
Authors | Kollmer, M. / Fandrich, M. | |||||||||
Funding support | Germany, 2items
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Citation | Journal: Nat Commun / Year: 2019 Title: Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer's brain tissue. Authors: Marius Kollmer / William Close / Leonie Funk / Jay Rasmussen / Aref Bsoul / Angelika Schierhorn / Matthias Schmidt / Christina J Sigurdson / Mathias Jucker / Marcus Fändrich / Abstract: The formation of Aβ amyloid fibrils is a neuropathological hallmark of Alzheimer's disease and cerebral amyloid angiopathy. However, the structure of Aβ amyloid fibrils from brain tissue is poorly ...The formation of Aβ amyloid fibrils is a neuropathological hallmark of Alzheimer's disease and cerebral amyloid angiopathy. However, the structure of Aβ amyloid fibrils from brain tissue is poorly understood. Here we report the purification of Aβ amyloid fibrils from meningeal Alzheimer's brain tissue and their structural analysis with cryo-electron microscopy. We show that these fibrils are polymorphic but consist of similarly structured protofilaments. Brain derived Aβ amyloid fibrils are right-hand twisted and their peptide fold differs sharply from previously analyzed Aβ fibrils that were formed in vitro. These data underscore the importance to use patient-derived amyloid fibrils when investigating the structural basis of the disease. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6shs.cif.gz | 149.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6shs.ent.gz | 123.7 KB | Display | PDB format |
PDBx/mmJSON format | 6shs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6shs_validation.pdf.gz | 761.1 KB | Display | wwPDB validaton report |
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Full document | 6shs_full_validation.pdf.gz | 773.9 KB | Display | |
Data in XML | 6shs_validation.xml.gz | 20.2 KB | Display | |
Data in CIF | 6shs_validation.cif.gz | 30 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sh/6shs ftp://data.pdbj.org/pub/pdb/validation_reports/sh/6shs | HTTPS FTP |
-Related structure data
Related structure data | 10204MC 4864C 4866C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein/peptide | Mass: 4335.852 Da / Num. of mol.: 12 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Organ: BRAIN / Tissue: meninges / References: UniProt: P05067 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: HELICAL ARRAY / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: meninges / Type: TISSUE / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) / Organ: brain / Tissue: meninges |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: C-flat-1.2/1.3 |
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 294 K |
-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 magnification: 105000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 24 sec. / Electron dose: 40.9 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 3027 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 12282 / Symmetry type: POINT | |||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |