[English] 日本語
Yorodumi
- EMDB-21501: Amyloid-beta(1-40) fibril derived from Alzheimer's disease cortic... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-21501
TitleAmyloid-beta(1-40) fibril derived from Alzheimer's disease cortical tissue
Map data
Sampleamyloid-beta(1-40) fibrils derived from human AD brain:
Amyloid-beta precursor protein
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)
Methodhelical reconstruction / cryo EM / Resolution: 2.77 Å
AuthorsGhosh U / Thurber KR / 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 ReportSummary, Full report, XML, About validation report
History
DepositionMar 2, 2020-
Header (metadata) releaseApr 1, 2020-
Map releaseJan 13, 2021-
UpdateJan 27, 2021-
Current statusJan 27, 2021Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.021
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.021
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6w0o
  • Surface level: 0.021
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6w0o
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_21501.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 400 pix.
= 432. Å
1.08 Å/pix.
x 400 pix.
= 432. Å
1.08 Å/pix.
x 400 pix.
= 432. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.08 Å
Density
Contour LevelBy AUTHOR: 0.021 / Movie #1: 0.021
Minimum - Maximum-0.0682921 - 0.13522795
Average (Standard dev.)-3.7405164e-06 (±0.0031375533)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 432.00003 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.081.081.08
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z432.000432.000432.000
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ400400400
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-0.0680.135-0.000

-
Supplemental data

-
Segmentation: #1

Fileemd_21501_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

-
Sample components

-
Entire amyloid-beta(1-40) fibrils derived from human AD brain

EntireName: amyloid-beta(1-40) fibrils derived from human AD brain
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.
Number of components: 2

-
Component #1: protein, amyloid-beta(1-40) fibrils derived from human AD brain

ProteinName: amyloid-beta(1-40) fibrils derived from human AD brain
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.
Recombinant expression: No
MassExperimental: 29 MDa
SourceSpecies: Homo sapiens (human)

-
Component #2: protein, Amyloid-beta precursor protein

ProteinName: Amyloid-beta precursor protein / Number of Copies: 6 / Recombinant expression: No
MassTheoretical: 4.335852 kDa
SourceSpecies: Homo sapiens (human)

-
Experimental details

-
Sample preparation

SpecimenSpecimen state: Filament / Method: cryo EM
Helical parametersAxial symmetry: C1 (asymmetric) / Delta z: 2.45 Å / Delta phi: 179.66 %deg;
Sample solutionSpecimen conc.: 0.45 mg/mL
Buffer solution: 10 mM phosphate buffer with 0.01% NaN3 to avoid microbial contamination. Buffers were filtered to avoid contamination.
pH: 7.4
Support filmThe grids were checked in microscope prior to use.
VitrificationInstrument: LEICA PLUNGER / Cryogen name: ETHANE / Temperature: 293 K / Humidity: 90 %
Details: The grids were preblotted for 10 seconds and blotted for 6 seconds before plunging..

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: TFS KRIOS
Details: Preliminary grid screening was done manually in FEI T12.
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 73.5 e/Å2 / Illumination mode: FLOOD BEAM
LensMagnification: 130000 X (nominal) / Cs: 2.7 mm / Imaging mode: BRIGHT FIELD / Defocus: -500.0 - -3000.0 nm / Energy filter: GIF Quantum LS
Specimen HolderModel: FEI TITAN KRIOS AUTOGRID HOLDER
CameraDetector: GATAN K2 QUANTUM (4k x 4k)

-
Image acquisition

Image acquisitionNumber of digital images: 1337

-
Image processing

ProcessingMethod: helical reconstruction
Details: The selected images were corrected for gain. The gain reference was not rotated or flipped.
3D reconstructionAlgorithm: FOURIER SPACE / Software: RELION
CTF correction: The correction was done in Gctf and is corrected for amplitude. Per -particle CTF refinement was done prior to final reconstruction.
Resolution: 2.77 Å / Resolution method: FSC 0.143 CUT-OFF
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.
FSC plot (resolution estimation)

-
Atomic model buiding

Modeling #1Refinement 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).
Output model

+
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