[English] 日本語
Yorodumi
- PDB-6w0o: Amyloid-beta(1-40) fibril derived from Alzheimer's disease cortic... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6w0o
TitleAmyloid-beta(1-40) fibril derived from Alzheimer's disease cortical tissue
ComponentsAmyloid-beta precursor protein
KeywordsPROTEIN FIBRIL / amyloid-beta / Alzheimer's disease
Function / homology
Function and homology information


amylin binding / acetylcholine receptor activator activity / positive regulation of protein import / regulation of acetylcholine-gated cation channel activity / positive regulation of G protein-coupled receptor internalization / positive regulation of cellular response to thapsigargin / positive regulation of cellular response to tunicamycin / amyloid-beta complex / regulation of response to calcium ion / signaling receptor activator activity ...amylin binding / acetylcholine receptor activator activity / positive regulation of protein import / regulation of acetylcholine-gated cation channel activity / positive regulation of G protein-coupled receptor internalization / positive regulation of cellular response to thapsigargin / positive regulation of cellular response to tunicamycin / amyloid-beta complex / regulation of response to calcium ion / signaling receptor activator activity / positive regulation of response to endoplasmic reticulum stress / growth cone lamellipodium / positive regulation of 1-phosphatidylinositol-3-kinase activity / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / endosome to plasma membrane transport vesicle / microglia development / regulation of epidermal growth factor-activated receptor activity / regulation of dendritic spine maintenance / protein trimerization / positive regulation of endothelin production / negative regulation of blood circulation / mating behavior / lipoprotein particle / regulation of amyloid-beta clearance / positive regulation of oxidative stress-induced neuron death / smooth endoplasmic reticulum calcium ion homeostasis / negative regulation of mitochondrion organization / regulation of amyloid fibril formation / regulation of spontaneous synaptic transmission / tumor necrosis factor production / axon midline choice point recognition / synaptic growth at neuromuscular junction / astrocyte activation involved in immune response / cellular process / regulation of synapse structure or activity / positive regulation of amyloid fibril formation / modulation of excitatory postsynaptic potential / PTB domain binding / intermediate-density lipoprotein particle / astrocyte projection / positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process / Golgi-associated vesicle / ciliary rootlet / peptidase activator activity / positive regulation of G protein-coupled receptor signaling pathway / axo-dendritic transport / activation of MAPKKK activity / positive regulation of protein metabolic process / positive regulation of cell activation / main axon / RAGE receptor binding / neuron remodeling / negative regulation of protein localization to nucleus / high-density lipoprotein particle / positive regulation of T cell migration / frizzled binding / response to yeast / heparan sulfate binding / heparan sulfate proteoglycan binding / lipoprotein metabolic process / dendrite development / COPII-coated ER to Golgi transport vesicle / nuclear envelope lumen / suckling behavior / regulation of presynapse assembly / positive regulation of membrane protein ectodomain proteolysis / positive regulation of chemokine production => GO:0032722 / positive regulation of protein kinase A signaling / negative regulation of pri-miRNA transcription by RNA polymerase II / mRNA polyadenylation / positive regulation of monocyte chemotaxis / smooth endoplasmic reticulum / acetylcholine receptor binding / low-density lipoprotein particle receptor binding / antifungal humoral response / negative regulation of long-term synaptic potentiation / cellular copper ion homeostasis / growth factor receptor binding / neuromuscular process controlling balance / positive regulation of tumor necrosis factor production => GO:0032760 / apolipoprotein binding / positive regulation of amyloid-beta formation / negative regulation of neuron differentiation / transition metal ion binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / regulation of toll-like receptor signaling pathway / associative learning / trans-Golgi network membrane / regulation of NMDA receptor activity / positive regulation of tau-protein kinase activity / positive regulation of excitatory postsynaptic potential / regulation of Wnt signaling pathway / RNA polymerase II core promoter sequence-specific DNA binding / spindle midzone / clathrin-coated pit / chemoattractant activity / regulation of peptidyl-tyrosine phosphorylation / synapse organization
Amyloidogenic glycoprotein, copper-binding domain superfamily / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Beta-amyloid precursor protein C-terminal / Pancreatic trypsin inhibitor Kunitz domain superfamily / Amyloid-beta precursor protein / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Amyloidogenic glycoprotein, E2 domain ...Amyloidogenic glycoprotein, copper-binding domain superfamily / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Beta-amyloid precursor protein C-terminal / Pancreatic trypsin inhibitor Kunitz domain superfamily / Amyloid-beta precursor protein / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Amyloidogenic glycoprotein, E2 domain / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, copper-binding / Proteinase inhibitor I2, Kunitz, conserved site / PH-like domain superfamily / Amyloidogenic glycoprotein, intracellular domain, conserved site / Amyloidogenic glycoprotein, copper-binding domain conserved site / Pancreatic trypsin inhibitor Kunitz domain / Amyloidogenic glycoprotein, amyloid-beta peptide
Amyloid-beta precursor protein
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / SOLID-STATE NMR / helical reconstruction / simulated annealing / cryo EM / Resolution: 2.77 Å
AuthorsGhosh, U. / Thurber, K.R. / Tycko, R.
CitationJournal: Proc Natl Acad Sci U S A / Year: 2021
Title: Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue.
Authors: Ujjayini Ghosh / Kent R Thurber / Wai-Ming Yau / Robert Tycko /
Abstract: Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report ...Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report the molecular structure of a specific fibril polymorph, formed by 40-residue Aβ peptides (Aβ40), that is derived from cortical tissue of an AD patient by seeded fibril growth. The structure is determined from cryogenic electron microscopy (cryoEM) images, supplemented by mass-per-length (MPL) measurements and solid-state NMR (ssNMR) data. Previous ssNMR studies with multiple AD patients had identified this polymorph as the most prevalent brain-derived Aβ40 fibril polymorph from typical AD patients. The structure, which has 2.8-Å resolution according to standard criteria, differs qualitatively from all previously described Aβ fibril structures, both in its molecular conformations and its organization of cross-β subunits. Unique features include twofold screw symmetry about the fibril growth axis, despite an MPL value that indicates three Aβ40 molecules per 4.8-Å β-sheet spacing, a four-layered architecture, and fully extended conformations for molecules in the central two cross-β layers. The cryoEM density, ssNMR data, and MPL data are consistent with β-hairpin conformations for molecules in the outer cross-β layers. Knowledge of this brain-derived fibril structure may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors with greater diagnostic and therapeutic utility.
Validation Report
SummaryFull reportAbout validation report
History
DepositionMar 2, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 13, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 27, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.pdbx_database_id_DOI ..._citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-21501
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-21501
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
1: Amyloid-beta precursor protein
2: Amyloid-beta precursor protein
3: Amyloid-beta precursor protein
4: Amyloid-beta precursor protein
5: Amyloid-beta precursor protein
6: Amyloid-beta precursor protein


Theoretical massNumber of molelcules
Total (without water)26,0156
Polymers26,0156
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy, negative-stain TEM, unstained TEM, atomic force microscopy, cryoEM, solid state NMR, etc.
  • Download structure data
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area13490 Å2
ΔGint-83 kcal/mol
Surface area10060 Å2
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / 60structures with the least restraint violations
RepresentativeModel #1lowest energy
SymmetryHelical symmetry: (Circular symmetry: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 6 / Rise per n subunits: 2.45 Å / Rotation per n subunits: 179.66 °)

-
Components

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


Mass: 4335.852 Da / Num. of mol.: 6 / Fragment: UNP residues 653-692 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P05067

-
Experimental details

-
Experiment

Experiment
Method
ELECTRON MICROSCOPY
SOLID-STATE NMR
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction
NMR experiment
Conditions-IDExperiment-IDSolution-IDSample stateSpectrometer-IDType
111anisotropic13D NCACX
121anisotropic13D NCOCX
131anisotropic13D CANCX
141anisotropic13D CONCX
151anisotropic12D 13C-13C

-
Sample preparation

ComponentName: amyloid-beta(1-40) fibrils derived from human AD brain
Type: COMPLEX
Details: Fibrils produced by seeded growth using amyloid-beta in brain extract as the source of seeds. CryoEM and solid state NMR measurements were performed on second-generation seeded fibrils.
Entity ID: #1 / Source: NATURAL
Molecular weightValue: 29 kDa/nm / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
Details: 10 mM phosphate buffer with 0.01% NaN3 to avoid microbial contamination. Buffers were filtered to avoid contamination.
Buffer componentConc.: 10 mM / Name: Phosphate buffer / Formula: Na2HPO4/NaH2PO4
SpecimenConc.: 0.45 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Protein exists in solution as amyloid fibrils of varying lengths.
Specimen supportDetails: The grids were checked in microscope prior to use. / Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: LEICA PLUNGER / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 293 K
Details: The grids were preblotted for 10 seconds and blotted for 6 seconds before plunging.
DetailsType: fibrous protein
Contents: 100 uM U-15N,13C amyloid-beta(1-40), phosphate buffer
Details: lyophilized, rehydrated in MAS rotor, 100 uM concentration prior to pelleting
Label: U-labeled fibrils / Solvent system: phosphate buffer
SampleConc.: 100 uM / Component: amyloid-beta(1-40) / Isotopic labeling: U-15N,13C
Sample conditionsDetails: pelleted, lyophilized, rehydrated in MAS rotor / Ionic strength: 10 mM / Label: conditions_1 / pH: 7.4 / PH err: 0.05 / Pressure: 1 atm / Temperature: 297 K / Temperature err: 2

-
Data collection

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Details: Preliminary grid screening was done manually in FEI T12.
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 130000 X / Nominal defocus max: -3000 nm / Nominal defocus min: -500 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Model: FEI TITAN KRIOS AUTOGRID HOLDER / Residual tilt: 6 mradians
Image recordingAverage exposure time: 10 sec. / Electron dose: 73.5 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1337
EM imaging opticsEnergyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV
Image scansMovie frames/image: 50 / Used frames/image: 1-50
NMR spectrometerType: Varian InfinityPlus / Manufacturer: Varian / Model: InfinityPlus / Field strength: 600 MHz

-
Processing

EM software
IDNameVersionCategoryDetails
1RELION3particle selectionmanual picking
2SerialEMv3.7image acquisition
4GctfCTF correction
7Coot0.8.9model fittingmodel was built manually
9X-PLOR2.53model refinement
10RELION3initial Euler assignment
11MATLABinitial Euler assignment
13RELIONcustomclassificationmodified from 3.0-beta
14RELIONcustom3D reconstructionmodified from 3.0-beta
Image processingDetails: The selected images were corrected for gain. The gain reference was not rotated or flipped.
CTF correctionDetails: The correction was done in Gctf and is corrected for amplitude. Per -particle CTF refinement was done prior to final reconstruction.
Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Helical symmertyAngular rotation/subunit: 179.66 ° / Axial rise/subunit: 2.45 Å / Axial symmetry: C1
Particle selectionNum. of particles selected: 19790
Details: The particles were picked using Relion manual pick, with a 20A low pass filter and particle diameter of 30A.
3D reconstructionResolution: 2.77 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 14775 / Algorithm: FOURIER SPACE
Details: A modified version of RELION 3.0-beta was used for the reconstruction. The modified version allowed local averaging of the rotation angle. Final reconstruction used 2-fold screw symmetry.
Num. of class averages: 1 / Symmetry type: HELICAL
Atomic model buildingProtocol: AB INITIO MODEL / Space: REAL
Details: Xplor-NIH was used to combine EM density with phi/psi restraints from NMR chemical shifts (from Talos-N Version 4.21 Rev 2016.343.11.31).
NMR software
NameVersionDeveloperClassification
NMRPipeDelaglio, Grzesiek, Vuister, Zhu, Pfeifer and Baxprocessing
SparkyGoddardchemical shift assignment
X-PLOR NIH2.53Schwieters, Kuszewski, Tjandra and Clorerefinement
RefinementMethod: simulated annealing / Software ordinal: 3
Details: phi/psi from TalosN & EM density used as restraints
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the least restraint violations
Conformers calculated total number: 60 / Conformers submitted total number: 10

+
About Yorodumi

-
News

-
Aug 12, 2020. New: Covid-19 info

New: Covid-19 info

  • 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. New: 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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

Read more

-
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.

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