[English] 日本語
Yorodumi
- PDB-8bfa: Sarkosyl-extracted AppNL-G-F Abeta42 fibril structure -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8bfa
TitleSarkosyl-extracted AppNL-G-F Abeta42 fibril structure
ComponentsAmyloid-beta precursor protein
KeywordsPROTEIN FIBRIL / Amyloid / fibril / helical / cross-beta / beta amyloid / ex vivo / arctic mutant / alzheimers disease
Function / homology
Function and homology information


cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / NMDA selective glutamate receptor signaling pathway / 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 ...cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / NMDA selective glutamate receptor signaling pathway / 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 / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / COPII-coated ER to Golgi transport vesicle / suckling behavior / nuclear envelope lumen / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / The NLRP3 inflammasome / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / negative regulation of long-term synaptic potentiation / regulation of presynapse assembly / transition metal ion binding / regulation of multicellular organism growth / negative regulation of neuron differentiation / intracellular copper ion homeostasis / ECM proteoglycans / positive regulation of T cell migration / spindle midzone / smooth endoplasmic reticulum / Purinergic signaling in leishmaniasis infection / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / clathrin-coated pit / positive regulation of chemokine production / forebrain development / Notch signaling pathway / neuron projection maintenance / Mitochondrial protein degradation / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / cholesterol metabolic process / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / response to interleukin-1 / extracellular matrix organization / positive regulation of mitotic cell cycle / axonogenesis / adult locomotory behavior / platelet alpha granule lumen / trans-Golgi network membrane / learning / positive regulation of interleukin-1 beta production / dendritic shaft / positive regulation of peptidyl-threonine phosphorylation / positive regulation of long-term synaptic potentiation / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / serine-type endopeptidase inhibitor activity / neuromuscular junction / visual learning / recycling endosome / cognition / Golgi lumen / positive regulation of inflammatory response / positive regulation of interleukin-6 production / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / endocytosis / cellular response to amyloid-beta / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle / Platelet degranulation / apical part of cell
Similarity search - Function
Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site ...Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminus / Amyloid precursor protein (APP) intracellular domain signature. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Amyloid A4 N-terminal heparin-binding / E2 domain of amyloid precursor protein / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / amyloid A4 / Amyloidogenic glycoprotein / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / BPTI/Kunitz family of serine protease inhibitors. / Pancreatic trypsin inhibitor Kunitz domain / Kunitz/Bovine pancreatic trypsin inhibitor domain / Pancreatic trypsin inhibitor (Kunitz) family profile. / Pancreatic trypsin inhibitor Kunitz domain superfamily / PH-like domain superfamily
Similarity search - Domain/homology
Amyloid-beta precursor protein
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3 Å
AuthorsWilkinson, M. / Leistner, C. / Burgess, A. / Goodfellow, S. / Deuchars, S. / Ranson, N.A. / Radford, S.E. / Frank, R.A.W.
Funding support United Kingdom, 2items
OrganizationGrant numberCountry
Wellcome Trust United Kingdom
Medical Research Council (MRC, United Kingdom) United Kingdom
CitationJournal: Nat Commun / Year: 2023
Title: The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain.
Authors: Conny Leistner / Martin Wilkinson / Ailidh Burgess / Megan Lovatt / Stanley Goodbody / Yong Xu / Susan Deuchars / Sheena E Radford / Neil A Ranson / René A W Frank /
Abstract: Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. ...Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the in situ molecular architecture of Aβ fibrils in the App familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Aβ fibrils. We show that in-tissue Aβ fibrils are arranged in a lattice or parallel bundles, and are interdigitated by subcellular compartments, extracellular vesicles, extracellular droplets and extracellular multilamellar bodies. The Arctic Aβ fibril differs significantly from an earlier App fibril structure, indicating a striking effect of the Arctic mutation. These structural data also revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises β-amyloid plaque pathology.
History
DepositionOct 24, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 31, 2023Provider: repository / Type: Initial release
Revision 1.1Jul 24, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond / em_admin / Item: _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Amyloid-beta precursor protein
B: Amyloid-beta precursor protein
C: Amyloid-beta precursor protein
D: Amyloid-beta precursor protein
E: Amyloid-beta precursor protein
F: Amyloid-beta precursor protein
G: Amyloid-beta precursor protein
H: Amyloid-beta precursor protein
I: Amyloid-beta precursor protein
J: Amyloid-beta precursor protein


Theoretical massNumber of molelcules
Total (without water)44,48010
Polymers44,48010
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, mass spectrometry, 50% Abeta1-42, 30% Abeta1-38
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area31870 Å2
ΔGint-117 kcal/mol
Surface area14550 Å2

-
Components

#1: Protein/peptide
Amyloid-beta precursor protein / APP / ABPP / APPI / Alzheimer disease amyloid A4 protein homolog / Alzheimer disease amyloid ...APP / ABPP / APPI / Alzheimer disease amyloid A4 protein homolog / Alzheimer disease amyloid protein / Amyloid precursor protein / Amyloid-beta (A4) precursor protein / Amyloid-beta A4 protein / Cerebral vascular amyloid peptide / CVAP / PreA4 / Protease nexin-II / PN-II


Mass: 4448.025 Da / Num. of mol.: 10 / Source method: isolated from a natural source
Details: App^NL-G-F, humanised abeta42 with arctic mutation (E22G), processed form of APP cleaved in the brain
Source: (natural) Mus musculus (house mouse) / Tissue: Brain / References: UniProt: P05067

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

-
Sample preparation

ComponentName: Sarkosyl-extracted AppNL-G-F Abeta42 fibril / Type: COMPLEX / Details: Fibrils purified from mouse brain / Entity ID: all / Source: NATURAL
Molecular weightValue: 4.441 kDa/nm / Experimental value: YES
Source (natural)Organism: Mus musculus (house mouse) / Tissue: Brain
Buffer solutionpH: 7.4
Buffer component
IDConc.NameFormulaBuffer-ID
150 mMsodium chlorideNaCl1
220 mMTris-HCl1
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Sarkosyl-insoluble fibrils from App^NL-G-F mouse brain
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 277 K / Details: 6s blot

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 96000 X / Nominal defocus max: 3100 nm / Nominal defocus min: 1600 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE
Specimen holderSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 8 sec. / Electron dose: 52 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2428
Details: 1925 raw EER frames were collected per image and combined into 40 fractions for processing

-
Processing

EM software
IDNameVersionCategory
1crYOLOparticle selection
2EPUimage acquisition
4CTFFINDCTF correction
7Cootmodel fitting
9RELION4initial Euler assignment
10RELION4final Euler assignment
11RELION4classification
12RELION43D reconstruction
13PHENIX1.17model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Helical symmertyAngular rotation/subunit: 179.352 ° / Axial rise/subunit: 2.418 Å / Axial symmetry: C1
Particle selectionNum. of particles selected: 63680
Details: Manually picked a subset of images to train a model for automatic fibril segment picking in crYOLO
3D reconstructionResolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2568 / Symmetry type: HELICAL
Atomic model buildingB value: 89 / Protocol: AB INITIO MODEL / Space: REAL / Target criteria: Correlation coefficient

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more